Kidney Cancer

Overview

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 10 March, 2017 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (94)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

GeneLocationAliasesNotesTopicPapers
VHL 3p25.3 RCA1, VHL1, pVHL, HRCA1 -VHL and Kidney Cancer
477
HIF1A 14q23.2 HIF1, MOP1, PASD8, HIF-1A, bHLHe78, HIF-1alpha, HIF1-ALPHA -HIF1A and Kidney Cancer
148
MTOR 1p36.2 FRAP, FRAP1, FRAP2, RAFT1, RAPT1 -MTOR and Renal Cell Carcinoma
96
FLCN 17p11.2 BHD, FLCL -FLCN and Kidney Cancer
93
MET 7q31 HGFR, AUTS9, RCCP2, c-Met -C-MET and Renal Cell Carcinoma
92
PRCC 1q21.1 TPRC, RCCP1 Translocation
-t(X;1)(p11;q21) in Papillary Renal Cell Carcinoma
-PRCC and Renal Cell Carcinoma
87
FH 1q42.1 MCL, FMRD, LRCC, HLRCC, MCUL1 -FH and Kidney Cancer
77
TSC2 16p13.3 LAM, TSC4, PPP1R160 -TSC2 and Kidney Cancer
69
PAX8 2q13 -PAX8 and Kidney Cancer
62
CA9 9p13.3 MN, CAIX -CA9 and Kidney Cancer
59
BAP1 3p21.1 UCHL2, hucep-6, HUCEP-13 -BAP1 and Renal Cell Carcinoma
47
TFEB 6p21 TCFEB, BHLHE35, ALPHATFEB -TFEB and Kidney Cancer
43
TSC1 9q34 LAM, TSC -TSC1 and Kidney Cancer
41
ACHE 7q22 YT, ACEE, ARACHE, N-ACHE -ACHE and Kidney Cancer
40
IFNA2 9p22 IFNA, INFA2, IFNA2B, IFN-alphaA -IFNA2 and Kidney Cancer
40
IFNA7 9p22 IFNA-J, IFN-alphaJ -IFNA7 and Kidney Cancer
40
IFNA17 9p22 IFNA, INFA, LEIF2C1, IFN-alphaI -IFNA17 and Kidney Cancer
40
PAX2 10q24 FSGS7, PAPRS -PAX2 and Kidney Cancer
37
SMARCB1 22q11.23 RDT, INI1, SNF5, Snr1, BAF47, MRD15, RTPS1, Sfh1p, hSNFS, SNF5L1, SWNTS1, PPP1R144 -SMARCB1 and Kidney Cancer
31
MITF 3p14.2-p14.1 MI, WS2, CMM8, WS2A, bHLHe32 -MITF and Kidney Cancer
31
PBRM1 3p21 PB1, BAF180 -PBRM1 and Renal Cell Carcinoma
30
SLC2A1 1p34.2 PED, DYT9, GLUT, DYT17, DYT18, EIG12, GLUT1, HTLVR, GLUT-1, GLUT1DS -GLUT1 expression in Kidney Cancer
27
SDHB 1p36.1-p35 IP, SDH, CWS2, PGL4, SDH1, SDH2, SDHIP -SDHB and Kidney Cancer
27
CD99 Xp22.32 and Yp11.3 MIC2, HBA71, MIC2X, MIC2Y, MSK5X -CD99 and Kidney Cancer
26
SETD2 3p21.31 HYPB, SET2, HIF-1, HIP-1, KMT3A, HBP231, HSPC069, p231HBP -SETD2 and Renal Cell Carcinoma
23
AMACR 5p13 RM, RACE, CBAS4, AMACRD -AMACR and Renal Cell Carcinoma
23
CDKN1C 11p15.4 BWS, WBS, p57, BWCR, KIP2, p57Kip2 -CDKN1C and Kidney Cancer
18
POLE 12q24.3 FILS, POLE1, CRCS12 -POLE and Kidney Cancer
15
ASPSCR1 17q25.3 TUG, ASPL, ASPS, RCC17, UBXD9, UBXN9, ASPCR1 -ASPSCR1 and Kidney Cancer
14
WT1-AS 11p13 WIT1, WIT-1, WT1AS, WT1-AS1 -WT1-AS and Kidney Cancer
13
NONO Xq13.1 P54, NMT55, NRB54, P54NRB, PPP1R114 -NONO and Kidney Cancer
9
KDM5C Xp11.22-p11.21 MRXJ, SMCX, MRX13, MRXSJ, XE169, MRXSCJ, JARID1C, DXS1272E -KDM5C and Kidney Cancer
9
ZEB2 2q22.3 SIP1, SIP-1, ZFHX1B, HSPC082, SMADIP1 -ZEB2 and Kidney Cancer
9
EPAS1 2p21-p16 HLF, MOP2, ECYT4, HIF2A, PASD2, bHLHe73 -EPAS1 and Renal Cell Carcinoma
8
HNF1B 17q12 FJHN, HNF2, LFB3, TCF2, HPC11, LF-B3, MODY5, TCF-2, VHNF1, HNF-1B, HNF1beta, HNF-1-beta -HNF1B and Renal Cell Carcinoma
8
EGLN3 14q13.1 PHD3, HIFPH3, HIFP4H3 -EGLN3 and Kidney Cancer
8
RNF139 8q24 RCA1, TRC8, HRCA1 Translocation
-t(3;8)(p14.2;q24.1) in Hereditary Renal Cell Carcinoma
-RNF139 and Kidney Cancer
7
SDHA 5p15 FP, PGL5, SDH1, SDH2, SDHF, CMD1GG -SDHA and Kidney Cancer
7
CITED1 Xq13.1 MSG1 -CITED1 and Kidney Cancer
7
MEST 7q32 PEG1 -MEST and Kidney Cancer
7
KISS1 1q32 HH13, KiSS-1 -KISS1 and Renal Cell Carcinoma
6
KCNQ1OT1 11p15.5 LIT1, Kncq1, KvDMR1, KCNQ10T1, KCNQ1-AS2, KvLQT1-AS, NCRNA00012 -KCNQ1OT1 and Kidney Cancer
6
MEG3 14q32 GTL2, FP504, prebp1, PRO0518, PRO2160, LINC00023, NCRNA00023, onco-lncRNA-83 -MEG3 and Kidney Cancer
6
STIM1 11p15.4 GOK, TAM, TAM1, IMD10, STRMK, D11S4896E -STIM1 and Kidney Cancer
6
CXCR3 Xq13 GPR9, MigR, CD182, CD183, Mig-R, CKR-L2, CMKAR3, IP10-R -CXCR3 and Kidney Cancer
5
KISS1R 19p13.3 HH8, CPPB1, GPR54, AXOR12, KISS-1R, HOT7T175 -KISS1R and Renal Cell Carcinoma
5
LDHA 11p15.1 LDHM, GSD11, PIG19, HEL-S-133P -LDHA and Kidney Cancer
5
CA12 15q22 CAXII, HsT18816 -CA12 and Kidney Cancer
5
FABP7 6q22-q23 MRG, BLBP, FABPB, B-FABP, LTR2-FABP7 -FABP7 and Kidney Cancer
5
VIM 10p13 HEL113, CTRCT30 -VIM and Kidney Cancer
5
ACTB 7p22 BRWS1, PS1TP5BP1 -ACTB and Kidney Cancer
5
EGLN1 1q42.1 HPH2, PHD2, SM20, ECYT3, HALAH, HPH-2, HIFPH2, ZMYND6, C1orf12, HIF-PH2 -EGLN1 and Kidney Cancer
5
PPIA 7p13 CYPA, CYPH, HEL-S-69p -PPIA and Renal Cell Carcinoma
5
MINA 3q11.2 ROX, MDIG, NO52, MINA53 -MINA and Kidney Cancer
5
KRT7 12q13.13 K7, CK7, SCL, K2C7 -KRT7 and Kidney Cancer
5
KDM6A Xp11.2 UTX, KABUK2, bA386N14.2 -KDM6A and Kidney Cancer
4
EGR2 10q21.1 AT591, CMT1D, CMT4E, KROX20 -EGR2 and Kidney Cancer
4
CAST 5q15 BS-17, PLACK -CAST and Kidney Cancer
4
RBX1 22q13.2 ROC1, RNF75, BA554C12.1 -RBX1 and Kidney Cancer
4
TGFBI 5q31 CSD, CDB1, CDG2, CSD1, CSD2, CSD3, EBMD, LCD1, BIGH3, CDGG1 -TGFBI and Kidney Cancer
4
RAP1GAP 1p36.1-p35 RAPGAP, RAP1GA1, RAP1GAP1, RAP1GAPII -RAP1GAP and Kidney Cancer
4
CREB3L1 11p11.2 OASIS -CREB3L1 and Kidney Cancer
4
NNAT 20q11.2-q12 Peg5 -NNAT and Kidney Cancer
4
TNFSF15 9q32 TL1, TL1A, VEGI, VEGI192A -TNFSF1 and Kidney Cancer
4
RAB25 1q22 CATX-8, RAB11C -RAB25 and Kidney Cancer
4
SPINT2 19q13.1 PB, Kop, HAI2, DIAR3, HAI-2 -SPINT2 and Kidney Cancer
4
OSCAR 19q13.42 PIGR3, PIgR-3 -OSCAR and Kidney Cancer
4
CDCP1 3p21.31 CD318, TRASK, SIMA135 -CDCP1 and Kidney Cancer
4
SLIT2 4p15.2 SLIL3, Slit-2 -SLIT2 and Kidney Cancer
4
CLTC 17q23.1 Hc, CHC, CHC17, CLH-17, CLTCL2 -CLTC and Kidney Cancer
4
PKHD1 6p12.2 FCYT, ARPKD, TIGM1 -PKHD1 and Renal Cell Carcinoma
3
GATA5 20q13.33 GATAS, bB379O24.1 -GATA5 and Renal Cell Carcinoma
3
BNIP3L 8p21 NIX, BNIP3a -BNIP3L and Kidney Cancer
3
KRT19 17q21.2 K19, CK19, K1CS -KRT19 and Kidney Cancer
3
YWHAE 17p13.3 MDS, HEL2, MDCR, KCIP-1, 14-3-3E -YWHAE and Kidney Cancer
3
MIRLET7I 12q14.1 LET7I, let-7i, MIRNLET7I, hsa-let-7i -MicroRNA let-7i and Kidney Cancer
3
NOX4 11q14.3 KOX, KOX-1, RENOX -NOX4 and Kidney Cancer
3
HCK 20q11-q12 JTK9, p59Hck, p61Hck -HCK and Kidney Cancer
3
CD70 19p13 CD27L, CD27LG, TNFSF7 -CD70 and Renal Cell Carcinoma
3
CALCA 11p15.2 CT, KC, PCT, CGRP, CALC1, CGRP1, CGRP-I -CALCA and Kidney Cancer
3
MT1G 16q13 MT1, MT1K -MT1G and Kidney Cancer
3
CXCL11 4q21.2 IP9, H174, IP-9, b-R1, I-TAC, SCYB11, SCYB9B -CXCL11 and Kidney Cancer
3
IL16 15q26.3 LCF, NIL16, PRIL16, prIL-16 -IL16 and Kidney Cancer
2
SLC22A18 11p15.4 HET, ITM, BWR1A, IMPT1, TSSC5, ORCTL2, BWSCR1A, SLC22A1L, p45-BWR1A -SLC22A18 and Kidney Cancer
2
ARID2 12q12 p200, BAF200 -ARID2 and Kidney Cancer
2
SLC34A2 4p15.2 NPTIIb, NAPI-3B, NAPI-IIb -SLC34A2 and Kidney Cancer
2
VCAM1 1p32-p31 CD106, INCAM-100 -VCAM1 and Kidney Cancer
2
RARRES3 11q12.3 RIG1, TIG3, HRSL4, HRASLS4, PLA1/2-3 -RARRES3 and Kidney Cancer
2
IGF2-AS 11p15.5 PEG8, IGF2AS, IGF2-AS1 -IGF2-AS and Kidney Cancer
2
MIR10B 2q31.1 MIRN10B, mir-10b, miRNA10B, hsa-mir-10b -MIR10B and Kidney Cancer
1
PDGFRL 8p22-p21.3 PDGRL, PRLTS -PDGFRL and Kidney Cancer
1
KLLN 10q23 CWS4, KILLIN -KLLN and Kidney Cancer
1
FHIT 3p14.2 FRA3B, AP3Aase Translocation
-t(3;8)(p14.2;q24.1) in Hereditary Renal Cell Carcinoma
TFE3 Xp11.22 TFEA, RCCP2, RCCX1, bHLHe33 Translocation
-t(X;1)(p11;q21) in Papillary Renal Cell Carcinoma

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Recurrent Structural Abnormalities

Selected list of common recurrent structural abnormalities

Abnormality Type Gene(s)
t(3;8)(p14.2;q24.1) in Hereditary Renal Cell CarcinomaTranslocationFHIT (3p14.2)RNF139 (8q24)
t(X;1)(p11;q21) in Papillary Renal Cell CarcinomaTranslocationTFE3 (Xp11.22)PRCC (1q21.1)

This is a highly selective list aiming to capture structural abnormalies which are frequesnt and/or significant in relation to diagnosis, prognosis, and/or characterising specific cancers. For a much more extensive list see the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.

Latest Publications

Yang L, Zhao Z, Zhao S, et al.
The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis.
Cell Physiol Biochem. 2016; 40(6):1465-1472 [PubMed] Related Publications
BACKGROUND/AIMS: Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC.
METHODS: The potential relevant papers were searched via PubMed, Embase, EBSCO, CNKI, and Wanfang databases. The overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the relationship between VHL promoter hypermethylation and RCC.
RESULTS: Finally, a total of 1,998 RCC patients and 294 controls from 13 eligible articles were included in this meta-analysis. Under the fixed-effects model, the pooled OR from seven studies including 596 RCC and 294 nonmalignant samples showed that VHL promoter hypermethylation was significantly higher in cancer than in controls (OR = 7.93, 95% CI = 2.84- 22.15, P < 0.001). Subgroup analysis based on ethnic population and testing method revealed that hypermethylated VHL had a significantly similar OR value in different races and detection methodologies. No significant association was found between hypermethylated VHL and tumor grade, tumor stage, tumor size, histological types, and lymph node status in cancer (all P > 0.05). In the current study, there was no evidence of publication bias as determined by Egger's test (all P > 0.05).
CONCLUSIONS: In the investigated patients, VHL promoter hypermethylation, which may play an important role in carcinogenesis of RCC, is significantly associated with an increased risk of RCC. However, VHL promoter hypermethylation is not correlated with specific clinicopathological characteristics. Additional future studies are needed to confirm our results.

Zheng J, Wang L, Peng Z, et al.
Low level of PDZ domain containing 1 (PDZK1) predicts poor clinical outcome in patients with clear cell renal cell carcinoma.
EBioMedicine. 2017; 15:62-72 [PubMed] Free Access to Full Article Related Publications
Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In this study, samples from primary ccRCC tumor and their corresponding nontumor adjacent tissues (n=18) were analyzed by quantitative proteomic assay. Proteins downregulated in tumors were studied by GO and KEGG pathways enrichment analyses. Six proteins were found both downregulated and annotated with cell proliferation in ccRCC patients. Of these proteins, PDZK1 and FABP1 were also involved in the lipid metabolism pathway. The downregulation of PDZK1 was further validated in TCGA_KIRC dataset (n=532) and independent set (n=202). PDZK1 could discriminate recurrence, metastasis and prognosis between ccRCC patients. Low level of PDZK1 in both mRNA and protein was associated with reduced overall survival (OS) and disease-free survival (DFS) in two independent sets. In univariate and multivariate analyses, PDZK1 was defined as an independent prognostic factor for both OS and DFS. These findings indicated that low level of PDZK1 could predict poor clinical outcome in patients with ccRCC.

Iliev R, Fedorko M, Machackova T, et al.
Expression Levels of PIWI-interacting RNA, piR-823, Are Deregulated in Tumor Tissue, Blood Serum and Urine of Patients with Renal Cell Carcinoma.
Anticancer Res. 2016; 36(12):6419-6423 [PubMed] Related Publications
BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3% of adult malignancies. P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of naturally occurring, short non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. There were preliminary data published indicating that piR-823 expression is deregulated in circulating tumor cells and tumor tissue in gastric and kidney cancer, respectively.
PATIENTS AND METHODS: In our study, we analyzed piR-823 levels in 588 biological specimens: tumor tissue (N=153), adjacent renal parenchyma (N=121), blood serum (N=178) and urine (N=20) of patients undergoing nephrectomy for RCC; and in blood serum (N=101) and urine (N=15) of matched healthy controls. Expression levels of piR-823 were determined in all biological specimens by quantitative real-time polymerase chain reaction, compared in patients and controls, and correlated with clinicopathological features of RCC.
RESULTS: We identified a significant down-regulation of piR-823 in tumor tissue [p<0.0001, area under the curve (AUC)=0.7945]. On the contrary in blood serum and urine, the expression of piR-823 was significantly higher in patients with RCC compared to healthy individuals (p=0.0005, AUC=0.6264 and p=0.0157, AUC=0.7433, respectively). We further observed higher levels of piR-823 in tumor tissue to be associated with shorter disease-free survival of patients (p=0.0186) and a trend for higher piR-823 levels in serum to be associated with advanced clinical stages of RCC (p=0.0691). There were no other significant associations of piR-823 levels in any type of biological specimen with clinicopathological features of RCC.
CONCLUSION: piR-823 is down-regulated in tumor tissue, but positively correlated with worse outcome, indicating its complex role in RCC pathogenesis. In blood serum, piR-823 is up-regulated, but with unsatisfactory analytical performance. Preliminary data indicate the promising diagnostic utility of urinary piR-823 in patients with RCC.

Yu L, Li J, Xu S, et al.
An Xp11.2 translocation renal cell carcinoma with SMARCB1 (INI1) inactivation in adult end-stage renal disease: a case report.
Diagn Pathol. 2016; 11(1):98 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Xp11.2 translocation/transcription factor E3 (TFE3) rearrangement renal cell carcinoma (RCC) is a rare subtype of RCC with limited clinical and pathological data.
CASE PRESENTATION: Here we present an unusual high-grade Xp11.2 translocation RCC with a rhabdoid feature and SMARCB1 (INI1) inactivation in a 40-year-old man with end-stage kidney disease. The histological examination of the dissected left renal tumor showed an organoid architecture of the eosinophilic or clear neoplastic cells with necrosis and high mitotic activity. In some areas, non-adhesive tumor cells with eccentric nuclei were observed. Immunohistochemically (IHC), the tumor cells are positive for TFE3 and the renal tubular markers (PAX2 and PAX8), and completely negative for SMARCB1, an oncosuppressor protein. Break-apart florescence in situ hybridization and reverse transcription polymerase chain reaction confirmed TFE3 rearrangement on Xp11.2 and the presence of ASPSCR1-TFE3 fusion gene. DNA sequencing revealed a frameshift mutation in exon 4 of SMARCB1 gene.
CONCLUSION: It is important to recognize this rare RCC with both TFE3 rearrangement and SMARCB1 inactivation, as the prognosis and therapeutic strategies, particularly targeted therapies for such tumors, might be different.

Iinuma K, Kojima K, Okamoto K, Yuhara K
[A Case of Xp.11.2 Traslocational Renal Cell Carcinoma Diagnosed by Fluorescence in Situ Hybridization (FISH)].
Hinyokika Kiyo. 2016; 62(8):411-4 [PubMed] Related Publications
A 72-year-old woman was referred to our hospital with complaints of macro-hematuria. The radiographic evaluation including computed tomography (CT) and magnetic resonance imaging (MRI) suggested it to be renal cell carcinoma (RCC) in her right kidney. She underwent laparoscopic nephrectomy. We diagnosed her with renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion, based on pathological findings and break apart of transcription factor E3 (TFE3)by fluorescence in situ hybridization. She was free of recurrence at 8 months postoperatively.

Pompas-Veganzones N, Sandonis V, Perez-Lanzac A, et al.
Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.
Tumour Biol. 2016; 37(10):14301-14310 [PubMed] Related Publications
Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.

Luo F, Shi J, Shi Q, et al.
Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy.
Cell Physiol Biochem. 2016; 39(3):1051-67 [PubMed] Related Publications
Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs) are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2), the c-Jun N-terminal kinases (JNK), p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1). Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

Zhang HP, Zou J, Yin Y, et al.
High-resolution Melting PCR Analysis for Genotyping Lys109Arg and Gln223Arg in Patients with Renal Cell Carcinoma.
Ann Clin Lab Sci. 2016; 46(4):367-73 [PubMed] Related Publications
Although several studies have documented the role of leptin receptor gene polymorphisms in cancers, the association between leptin receptor gene polymorphisms and renal cell carcinoma (RCC) remains unknown. The aim of this study was to develop a high-resolution melting (HRM) approach for genotyping single nucleotide polymorphisms of leptin receptor gene on the LightCycler 480, and to explore the relation between polymorphisms of the leptin receptor gene and RCC. The study population consisted of 83 patients with renal cell carcinoma and 161 healthy control subjects. The Lys109Arg (A/G) and Gln223Arg (A/G) polymorphisms of leptin receptor gene were examined with HRM assay. Direct DNA sequencing and PCR-restriction fragment length polymorphisms were used as a reference method for genotyping Lys109Arg and Gln223Arg, respectively. Three genotypes of Lys109Arg or Gln223Arg were clearly distinguishable from the melting curve shapes with HRM assay. The data also showed the results of the direct DNA sequencing or PCR-restriction fragment length polymorphisms analysis were in complete concordance to genotyping results obtained by HRM (kappa=1.0). In addition, the data showed the G-G haplotype frequency was higher (p<0.05), and that the A-G (p<0.001) and G-A (p<0.01) haplotypes frequencies were lower in the RCC than controls. We developed a rapid, low cost, high-throughput and reliable single-tube technology for genotyping Lys109Arg and Gln223Arg polymorphisms. In addition, our data suggest that Lys109Arg and Gln223Arg gene polymorphisms are associated with RCC in Chinese Han studied population.

Fang L, Zhang M, Chen L, et al.
Downregulation of nucleolar and spindle-associated protein 1 expression suppresses cell migration, proliferation and invasion in renal cell carcinoma.
Oncol Rep. 2016; 36(3):1506-16 [PubMed] Related Publications
Nucleolar and spindle-associated protein 1 (NUSAP1) is a microtubule-binding protein that plays an essential role in mitosis and cancer. Previous studies have demonstrated that NUSAP1 expression is relatively elevated in several malignancies. However, the biological roles of NUSAP1 in renal cell carcinoma (RCC) remain unknown. In the present study, we firstly performed reverse transcription‑polymerase chain reaction (RT-PCR) and western blot analysis to reveal that the expression of NUSAP1 was relatively elevated in clear cell RCC (ccRCC) tissue specimens and RCC cell lines. Immunohistochemical analysis showed that upregulation of NUSAP1 was significantly correlated with Fuhrman grade (P<0.001), tumor size (P=0.016), clinical stage (P<0.001) and distant metastasis (P=0.023). Additionally, high expression of NUSAP1 was closely associated with a shorter overall survival time of the ccRCC patients (P=0.006). Furthermore, we investigated the biological behaviors of RCC cells in vitro, and we identified that NUSAP1 depletion inhibited RCC cell migration, proliferation and invasion, and apoptosis was induced and the cell cycle was arrested. On the basis of our studies, NUSAP1 was identified as a potential prognostic indicator and a novel therapeutic target for RCC patients.

Cheng X, Gan W, Zhang G, et al.
Clinical characteristics of XP11.2 translocation/TFE3 gene fusion renal cell carcinoma: a systematic review and meta-analysis of observational studies.
BMC Urol. 2016; 16(1):40 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) is a rare subtype of RCC which is firstly described as a distinct entity in 2004 so that clinical characteristics of Xp11.2 RCC in different gender and age are unknown. The purpose of systematic review and meta-analysis is to provide a comprehensive assessment on them.
METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies which evaluate the clinical characteristics of Xp11.2 RCC. The literature published between July 2004 and May 2014 was searched.
RESULTS: A total of 15 studies with 147 participants were included. The meta-analysis demonstrated that number of patients of all age in female was higher than in male with pooled OR of 3.93(95 % CI = 1.66-9.34). However, incidence of distant metastases (OR = 0.34, 95 % CI = 0.12-1.57) and lymphatic metastases (OR = 0.51, 95 % CI = 0.14-1.91), tumor stage (OR = 0.85, 95 % CI = 0.34-2.15) and overall survival (OS) (OR = 0.46, 95 % CI = 0.05-4.34) between male and female were comparable. Incidence in female was higher than in male with pooled OR of 5.13(95 % CI = 1.67-15.72) in adults, while in children no gender-related predominance (OR = 1.19, 95 % CI = 0.38-3.72) was observed. In addition, incidence of distant metastases (OR = 1.00, 95 % CI = 0.13-7.84) and lymphatic metastases (OR = 1.00, 95 % CI = 0.07-13.67) and tumor stage (OR = 1.94, 95 % CI = 0.20-19.03) between children and adults were comparable. Survival curves presented comparable outcomes between male and female (P = 0.707) as well as between children and adults (P = 0.383).
CONCLUSIONS: Female patients with Xp11.2 RCC in adults exhibit a high incidence compared to male, but not in children. Comparable clinical characteristics including incidence of distant and lymphatic metastases, tumor stage and prognosis is presented between male and female as well as between children and adults.

Xu JS, Bai YL, Zhang JX, et al.
[Polymorphism at the miR-502 binding site in the 3' untranslated region of SET8 gene is associated with the risk of clear cell renal cell carcinoma].
Zhonghua Zhong Liu Za Zhi. 2016; 38(6):476-80 [PubMed] Related Publications
OBJECTIVE: To investigate the relationship between single nucleotide polymorphism of SET8 gene and the risk of clear cell renal cell carcinoma (CCRCC).
METHODS: We selected 140 CCRCC patients and 130 healthy controls in this case-control study.Genotype of single nucleotide polymorphism (rs16917496) at the miR-502 binding site in the 3'UTR of SET8 mRNA in the CCRCC patients and healthy controls was tested and the association between genotype and risk of cancer was assessed. The expression of SET8 was determined by immunohistochemistry and the relationship between expression of SET8 and genotype of rs16917496 was analyzed.
RESULTS: In the control group, CC, CT and TT genotypes were found in 30, 32 and 68 persons, respectively, while in the CCRCC patients, CC, CT and TT genotypes were found in 14 , 47 and 79 cases, respectively.The frequencies of rs16917496 CT and TT genotypes in the CCRCC group were significantly higher than those in the control group (P<0.05). Compared with the CC genotype, patients with CT and TT genotypes were more susceptible to develop CCRCC (P<0.05). CT and TT genotypes of rs16917496 at the miR-502 binding site of the SET8 gene were associated with expression of SET8.
CONCLUSIONS: Genotype of the SNP rs16917496 at the miR-502 binding site in the 3' untranslated region of the SET8 gene is associated with the expression of SET8 protein. Analysis of genetic polymorphisms in miRNA binding sites may help to identify the subgroups of population susceptible to CCRCC.

Zhang M, Lu W, Huang Y, et al.
Downregulation of the long noncoding RNA TUG1 inhibits the proliferation, migration, invasion and promotes apoptosis of renal cell carcinoma.
J Mol Histol. 2016; 47(4):421-8 [PubMed] Related Publications
Long non-coding RNAs, a newly discovered category of noncoding genes, play a leading role in various biological processes, including tumorigenesis. In our study, we aimed to examine the TUG1 expression, and explore the influence of TUG1 silencing on cell proliferation and apoptosis in renal cell carcinoma (RCC) cell lines. The TUG1 expression level was detected using quantitative real-time PCR reverse transcription-polymerase chain reaction in 40 paired clear cell renal cell carcinoma (ccRCC) and adjacent paired normal tissues, as well as four RCC cell lines and one normal human proximal tubule epithelial cell line HK-2. Small interfering RNA was applied to suppress the TUG1 expression in RCC cell lines (A489 and A704). In vitro assays were conducted to further deliberate its potential functions in RCC progression. The relative TUG1 expression was significantly higher in ccRCC tissues compared to the adjacent normal renal tissues. In addition, higher TUG1 expression was equally detected in RCC cell lines (particularly in A498 and A704) compared to HK-2. The ccRCC specimens with higher TUG1 expression had a higher Fuhrman grade and larger tumor size than those with lower TUG1 expression. In vitro assays results suggested that knockdown of TUG1 suppressed RCC cells migration, invasion and proliferation, while the apoptosis process was activated. Our results indicate that TUG1 is identified as a novel oncogene in the morbid state of RCC, which potentially acts as a therapeutic target/biomarker in RCC. The graphic abstract of the present work.

Yang SX, Chen F, Zhang JW, et al.
IL-16 rs4778889 polymorphism contribution to the development of renal cell cancer in a Chinese population.
Genet Mol Res. 2016; 15(2) [PubMed] Related Publications
IL-16 plays an important role in affect the secretion of tumor-related inflammatory cytokines. We aimed to assess the role of interleukin-16 (IL-16) rs4778889 T/C and rs11556218 T/G polymorphisms in the occurrence of renal cell cancer (RCC). This study is composed of 274 RCC patients and 274 control subjects. Genotyping of polymorphisms was performed using polymerase chain reaction combined with restriction fragment length polymorphism analysis. All statistical analysis was carried out by the SPSS statistical software package, version 16.0 (SPSS Inc., Chicago, IL, USA). Using conditional logistic regression analysis, the TC and CC genotypes of rs4778889 exhibited a higher risk of RCC, with adjusted ORs (and 95%CIs) of 1.79 (1.23-2.62) and 2.67 (1.29-5.69), respectively. Moreover, under dominant and recessive models, individuals carried the rs4778889 polymorphism was exhibited elevated RCC risk, with adjusted ORs (and 95%CI) of 1.93 (1.35-2.76) and 2.11 (1.05-4.45), respectively. No significant differences were observed in rs11556218 genotype frequencies between the study groups. In conclusion, the results of our study reveal an association between the IL-16 rs4778889 polymorphism and heightened risk of RCC.

Wang X, Ding M, Yang Y, et al.
Personalized discovery of altered pathways in clear cell renal cell carcinoma using accumulated normal sample data.
J BUON. 2016 Mar-Apr; 21(2):390-8 [PubMed] Related Publications
PURPOSE: To identify altered pathways in an individual with clear cell renal cell carcinoma (ccRCC) using accumulated normal sample data.
METHODS: Gene expression data of E-GEOD-40435 was downloaded from the ArrayExpress database. Gene-level statistics of genes in tumor and normal samples were computed. Then, the Average Z method was applied to calculate the individual pathway aberrance score (iPAS). Subsequently, the significantly altered pathways in a ccRCC sample were identified using T-test based on the pathway statistics values of normal and ccRCC samples. Moreover, the identified altered pathways were verified through two methods: one was assessing classification capability for microarray data samples, and the other was computing the changed percentage of each pathway in ccRCC samples.
RESULTS: Based on the threshold, 886 altered pathways were identified in all samples. The most significant pathways were potassium transport channels, proton-coupled monocarboxylate transport, beta oxidation of octanoyl-CoA to hexanoyl-CoA, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. Additionally, iPAS separated ccRCC from normal controls with an accuracy of 0.980. Moreover, a total of 5 significant pathways with change in 100% ccRCC samples were extracted including proton-coupled monocarboxylate transport, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on.
CONCLUSIONS: iPAS is useful to predict marker pathways for ccRCC with a high accuracy. Pathways of proton-coupled monocarboxylate transport, and antigen presentation: folding, assembly and peptide loading of class I MHC might play crucial roles in ccRCC progression.

Dong L, Gao M, Hao WJ, et al.
Case Report of Birt-Hogg-Dubé Syndrome: Germline Mutations of FLCN Detected in Patients With Renal Cancer and Thyroid Cancer.
Medicine (Baltimore). 2016; 95(22):e3695 [PubMed] Free Access to Full Article Related Publications
Birt-Hogg-Dubé (BHD) is a rare autosomal dominant inherited syndrome that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. Here, the 2 patients we reported with renal cell carcinomas and dermatological features were suspected to be suffering from BHD syndrome. Blood samples of these patients were sent for whole exon sequencing performed by Sanger sequencing. Eight mutations, including 5 mutations, which were mapped in noncoding region, 1 synonymous mutation, and 2 missense mutations, were detected in the FLCN gene in both patients. The 2 missense mutations, predicted to be disease-causing mutation or affecting protein function by MutationTaster and SIFT, confirmed the diagnosis. In addition, the 2 patients were also affected with papillary thyroid cancer. Total thyroidectomy and prophylactic bilateral central lymph node dissection were performed for them and the BHD-2 also received lateral lymph node dissection. Pathology reports showed that the patients had lymph node metastasis in spite of small size of thyroid lesions.The 2 missense mutations, not reported previously, expand the mutation spectrum of FLCN gene associated with BHD syndrome. For the thyroid cancer patients with BHD syndrome, total thyroidectomy and prophylactic bilateral central lymph node dissection may be suitable and the neck ultrasound may benefit BHD patients and their family members.

Wu Y, Zhang N, Li K, et al.
Genetic scores based on risk-associated single nucleotide polymorphisms (SNPs) can reveal inherited risk of renal cell carcinoma.
Oncotarget. 2016; 7(14):18631-7 [PubMed] Free Access to Full Article Related Publications
The objective of this study was to evaluate whether renal cell carcinoma (RCC) risk-associated single nucleotide polymorphisms (SNPs) could reflect the individual inherited risks of RCC. A total of 346 RCC patients and 1,130 controls were recruited in this case-control study. Genetic scores were calculated for each individual based on the odds ratios and frequencies of risk-associated SNPs. Four SNPs were significantly associated with RCC in Chinese population. Two genetic score models were established, genetic score 1 (rs10054504, rs7023329 and rs718314) and genetic score 2 (rs10054504, rs7023329 and rs1049380). For genetic score 1, the individual likelihood of RCC with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 1 was 15.61%, 22.25% and 33.92% respectively (P-trend=6.88×10(-7)). For genetic score 2, individual with low (<0.8), medium (0.8-1.2) and high (≥1.2) genetic score 2 would have likelihood of RCC as 14.39%, 24.54% and 36.48%, respectively (P-trend=1.27×10(-10)). The area under the receiver operating curve (AUC) of genetic score 1 was 0.626, and AUC of genetic score 2 was 0.658. We concluded that genetic score can reveal personal risk and inherited risk of RCC, especially when family history is not available.

Das F, Dey N, Bera A, et al.
MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells.
J Biol Chem. 2016; 291(28):14662-76 [PubMed] Article available free on PMC after 08/07/2017 Related Publications
Elevated IGF-1/insulin-like growth factor-1 receptor (IGF-1R) autocrine/paracrine signaling in patients with renal cell carcinoma is associated with poor prognosis of the disease independent of their von Hippel-Lindau (VHL) status. Increased expression of IGF-1R in renal cancer cells correlates with their potency of tumor development and progression. The mechanism by which expression of IGF-1R is increased in renal carcinoma is not known. We report that VHL-deficient and VHL-positive renal cancer cells possess significantly decreased levels of mature, pre-, and pri-miR-214 than normal proximal tubular epithelial cells. We identified an miR-214 recognition element in the 3'UTR of IGF-1R mRNA and confirmed its responsiveness to miR-214. Overexpression of miR-214 decreased the IGF-1R protein levels, resulting in the inhibition of Akt kinase activity in both types of renal cancer cells. IGF-1 provoked phosphorylation and inactivation of PRAS40 in an Akt-dependent manner, leading to the activation of mTORC1 signal transduction to increase phosphorylation of S6 kinase and 4EBP-1. Phosphorylation-deficient mutants of PRAS40 and 4EBP-1 significantly inhibited IGF-1R-driven proliferation of renal cancer cells. Expression of miR-214 suppressed IGF-1R-induced phosphorylation of PRAS40, S6 kinase, and 4EBP-1, indicating inhibition of mTORC1 activity. Finally, miR-214 significantly blocked IGF-1R-forced renal cancer cell proliferation, which was reversed by expression of 3'UTR-less IGF-1R and constitutively active mTORC1. Together, our results identify a reciprocal regulation of IGF-1R levels and miR-214 expression in renal cancer cells independent of VHL status. Our data provide evidence for a novel mechanism for IGF-1R-driven renal cancer cell proliferation involving miR-214 and mTORC1.

Kuroda N, Yorita K, Nagasaki M, et al.
Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects.
Pol J Pathol. 2016; 67(1):3-7 [PubMed] Related Publications
Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH) is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD). The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB, SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene) has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

Lan TT, Keller-Ramey J, Fitzpatrick C, et al.
Unclassified renal cell carcinoma with tubulopapillary architecture, clear cell phenotype, and chromosome 8 monosomy: a new kid on the block.
Virchows Arch. 2016; 469(1):81-91 [PubMed] Related Publications
Accurate subtyping of renal cell carcinomas (RCCs) has become clinically important for therapy and prognostication. RCC subtypes are defined by distinct morphologic and immunohistochemical profiles, and in some instances recurrent cytogenetic and molecular properties. However, some tumors exhibit overlapping morphologic and immunophenotypic features, frequent enough to pose diagnostic dilemmas. This report concerns six histologically unusual RCCs that showed tubulopapillary architecture, clear cell phenotype, and non-diagnostic immunohistochemical profiles. Further investigation of these tumors utilized a single nucleotide polymorphism (SNP) microarray platform (OncoScan®, Affymetrix) that employed molecular inversion probe (MIP) technology to investigate genome-wide chromosomal copy number changes and loss of heterozygosity in formalin-fixed paraffin-embedded sections. The six tumors were assayed in parallel with and in comparison to RCC with typical morphologic or immunohistochemical features for a specific subtype (clear cell, clear cell papillary, and microphthalmia transcription factor (MiT) family translocation RCC). Three of the unusual RCCs showed a molecular signature of clear cell RCC and one of papillary RCC. The remaining two showed monosomy of chromosome 8. Those two cases were tested via next-generation sequencing, and no pathogenic variants were detected, including those in the genes VHL, PBRM1, SETD2, KDM5C, or BAP1. The addition of molecular investigations such as reported here as applied to histologically and immunohistochemically unusual RCC may help to define additional subtypes and contribute to the development of targeted therapy for renal cancer.

Li1 XH, Yang CZ, Wang J
Network spatio-temporal analysis predicts disease stage-related genes and pathways in renal cell carcinoma.
Genet Mol Res. 2016; 15(2) [PubMed] Related Publications
The purpose of this study was to screen the key genes and pathways of renal cell carcinoma (RCC) and lay the foundation for its diagnosis and therapy. Microarray data of normal subjects and RCC patients at different stages of disease were used to screen differentially expressed genes (DEGs). Based on the DEGs in the four disease stages, four co-expression networks were constructed using the Empirical Bayes method and hub genes were obtained by centrality analysis. The enriched pathways of the DEGs and the mutual hub genes in the cluster of each disease stage were investigated. The mutual hub genes of the four disease stages in RCC tissue were validated using reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. A total of 432 DEGs were screened, including 233 upregulated and 199 downregulated genes, by statistical analysis. Centrality analysis of co-expression networks in different disease stages suggested that PLXDC1, IKZF1, RUNX2, and RNF125 were mutual hub genes. Pathway analysis showed that the DEGs were significantly enriched in seven terms. The hub modules in stage I disease were significantly enriched in the complement coagulation cascade pathway and the hub modules of the other three disease stages were enriched in natural killer cell-mediated cytotoxicity. The expression levels of PLXDC1, IKZF1, RUNX2, and RNF125 were significantly different between normal subjects and RCC patients by RT-PCR and western blot. Our study revealed four hub genes (PLXDC1, IKZF1, RUNX2, and RNF125) and two biological pathways that might be underlying biomarkers involved in RCC.

Huang YQ, Guan H, Liu CH, et al.
Association between RASSF1A promoter methylation and renal cell cancer susceptibility: a meta-analysis.
Genet Mol Res. 2016; 15(2) [PubMed] Related Publications
Epigenetic inactivation of Ras-associated domain family 1A (RASSF1A) by hyper-methylation of its promoter region has been identified in various cancers. However, the role of RASSF1A in renal cancer has neither been thoroughly investigated nor reviewed. In this study, we reviewed and performed a meta-analysis of 13 published studies reporting correlations between methylation frequency of the RASSF1A promoter region and renal cancer risk. The odds ratios (ORs) of eligible studies and their corresponding 95% confidence intervals (95%CIs) were used to correlate RASSF1A promoter methylation with renal cell cancer risk and clinical or pathological variables, respectively. RASSF1A promoter methylation was significantly associated with the risk of renal cell cancer (OR = 19.35, 95%CI = 9.57-39.13). RASSF1A promoter methylation was significantly associated with pathological tumor grade (OR = 3.32, 95%CI = 1.55-7.12), and a possible positive correlation between RASSF1A promoter methylation status and tumor stage was noted (OR = 1.89, 95%CI = 1.00-3.56, P = 0.051). Overall, this meta-analysis demonstrated that RASSF1A promoter methylation is significantly associated with increased risk of renal cell cancer. RASSF1A promoter methylation frequency was positively correlated with pathological tumor grade, but not the clinical stage. This study showed that RASSF1A promoter methylation could be utilized to predict renal cell cancer prognosis.

Zhang S, Hong Z, Li Q, et al.
Effect of MicroRNA-218 on the viability, apoptosis and invasion of renal cell carcinoma cells under hypoxia by targeted downregulation of CXCR7 expression.
Biomed Pharmacother. 2016; 80:213-9 [PubMed] Related Publications
OBJECTIVE: To investigate the effect of microRNA-218 on the viability, apoptosis and invasion of renal cell carcinoma cells under hypoxia by targeted regulation of expression of chemokine receptor 7 (CXCR7).
METHODS: The expression of miR-218 in renal cell carcinoma cell lines under normal and hypoxia conditions, as well in normal renal tubular epithelial cells (HK2) was measured using RT-PCR. MiR-218 mimic and NC were transfected into renal cell carcinoma cell line ACHN using Lipofectamine™ 2000. The expression of miR-218 was analyzed using RT-PCR. The viability, apoptosis, migration and invasion of the transfected cells were assayed using the MTT assay, flow cytometry and transwell assays. The expression of CXCR7 was assayed using RT-PCR and Western blot. Luciferase reporter was used to verify the downstream target of miR-218.
RESULTS: The expression of miR-218 was lower than in renal cell carcinoma cell lines ACHN, 769-p and Caki-1 that in HK-2. The expression of miR-218 in the renal carcinoma cell lines was lower under hypoxia than under normal oxygen conditions. The expression of miR-218 in ACHN cells under normal and hypoxic conditions was significantly increased after transfection with miR-218 mimic. Compared with NC transfected cells under normal oxygen condition, the mimic-transfected cells had reduced viability, migration ability and invasion ability, and increased apoptosis, and mimic transfected-cells under hypoxia had significantly reduced viability, migration ability and invasion ability, and increased apoptosis. Overexpression of miR-218 mimic resulted in significant reduction in the expression of CXCR7 at protein and mRNA levels under normal and hypoxic conditions. Luciferase reporter assay confirmed that CXCR7 is the target protein of miR-218.
CONCLUSION: Up-regulation of miR-218 expression in renal cell carcinoma under hypoxia can result in significant and targeted down-regulation of CXCR7 expression, which could reduce cell viability, migration and invasion ability and induce apoptosis in the cancer cells.

Chang WS, Liao CH, Tsai CW, et al.
The Role of IL-10 Promoter Polymorphisms in Renal Cell Carcinoma.
Anticancer Res. 2016; 36(5):2205-9 [PubMed] Related Publications
BACKGROUND/AIM: Renal cell carcinoma (RCC) accounts for approximately 3% of all cancer-related mortalities worldwide and the risk factors for the development of RCC have not yet been fully elucidated. Mounting proteomic evidence suggests that inflammatory process plays a role in RCC etiology and interleukin-10 (IL-10) is an important immunosuppressive cytokine. However, little is known on the contribution of IL-10 genotypes to RCC. This study aimed at evaluating the contribution of IL-10 promoter A-1082G (rs1800896), T-819C (rs3021097), A-592C (rs1800872) genetic polymorphisms to the risk of RCC in Taiwan.
MATERIALS AND METHODS: Associations of the three IL-10 polymorphic genotypes with the risk of RCC were examined among 92 RCC patients and 580 age- and gender-matched cancer-free controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology.
RESULTS: The pilot results showed that the percentages of TT and TC for IL-10 T-819C genotypes were significantly higher in the RCC patient group than those in the healthy control group. The CC genotype carriers were of lower risk for RCC (odds ratio (OR)=0.33, 95% confidence interval (CI)=0.12-0.93, p=0.0369). There is no difference in the distribution of A-1082G or A-592C genotype between the RCC and control groups.
CONCLUSION: The CC genotype of IL-10 T-819C genotype may have a protective effect on RCC risk in Taiwan. Further investigation with larger sample size in addition to genotype-phenotype correlation and intracellular mechanisms are our future work.

Fu H, Liu Y, Xu L, et al.
Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma.
Medicine (Baltimore). 2016; 95(17):e3225 [PubMed] Article available free on PMC after 08/07/2017 Related Publications
Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC.The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan-Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram.In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy.MUC4 expression is an independent prognostic factor for OS in patients with ccRCC.

Kowalczyk AE, Krazinski BE, Godlewski J, et al.
SATB1 is Down-regulated in Clear Cell Renal Cell Carcinoma and Correlates with miR-21-5p Overexpression and Poor Prognosis.
Cancer Genomics Proteomics. 2016 May-Jun; 13(3):209-17 [PubMed] Related Publications
BACKGROUND: Altered expression of special AT-rich sequence binding protein 1 (SATB1) was reported in several types of human cancers. This study aimed to determine the expression levels of SATB1, as well as miR-21-5p -the post-transcriptional repressor of SATB1 expression- in clear cell renal cell carcinoma (ccRCC) and to investigate their association with the progression of ccRCC.
MATERIALS AND METHODS: Immunohistochemistry and quantitative polymerase chain reaction were used to assess the expression of SATB1 protein and mRNA as well as miR-21-5p in tumor and matched normal kidney tissues collected from 56 ccRCC patients.
RESULTS: Nuclear SATB1 immunoreactivity was elevated in ccRCC cells while its cytoplasmic expression was decreased. SATB1 mRNA level was down-regulated in ccRCC tissue and inversely correlated with the content of miR-21-5p. Down-regulation of SATB1 mRNA and up-regulation of miR-21-5p were associated with shorter patient survival.
CONCLUSION: Decreased expression of SATB1 in ccRCC may result from over-expressed miR-21-5p. Our data suggest that SATB1 may have a potential value as a prognostic marker in ccRCC.

Chowdhury B, Porter EG, Stewart JC, et al.
PBRM1 Regulates the Expression of Genes Involved in Metabolism and Cell Adhesion in Renal Clear Cell Carcinoma.
PLoS One. 2016; 11(4):e0153718 [PubMed] Article available free on PMC after 08/07/2017 Related Publications
Polybromo-1 (PBRM1) is a component of the PBAF (Polybromo-associated-BRG1- or BRM-associated factors) chromatin remodeling complex and is the second most frequently mutated gene in clear-cell renal cell Carcinoma (ccRCC). Mutation of PBRM1 is believed to be an early event in carcinogenesis, however its function as a tumor suppressor is not understood. In this study, we have employed Next Generation Sequencing to profile the differentially expressed genes upon PBRM1 re-expression in a cellular model of ccRCC. PBRM1 re-expression led to upregulation of genes involved in cellular adhesion, carbohydrate metabolism, apoptotic process and response to hypoxia, and a downregulation of genes involved in different stages of cell division. The decrease in cellular proliferation upon PBRM1 re-expression was confirmed, validating the functional role of PBRM1 as a tumor suppressor in a cell-based model. In addition, we identified a role for PBRM1 in regulating metabolic pathways known to be important for driving ccRCC, including the regulation of hypoxia response genes, PI3K signaling, glucose uptake, and cholesterol homeostasis. Of particular novelty is the identification of cell adhesion as a major downstream process uniquely regulated by PBRM1 expression. Cytoskeletal reorganization was induced upon PBRM1 reexpression as evidenced from the increase in the number of cells displaying cortical actin, a hallmark of epithelial cells. Genes involved in cell adhesion featured prominently in our transcriptional dataset and overlapped with genes uniquely regulated by PBRM1 in clinical specimens of ccRCC. Genes involved in cell adhesion serve as tumor suppressor and maybe involved in inhibiting cell migration. Here we report for the first time genes linked to cell adhesion serve as downstream targets of PBRM1, and hope to lay the foundation of future studies focusing on the role of chromatin remodelers in bringing about these alterations during malignancies.

Seles M, Hutterer GC, Kiesslich T, et al.
Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma.
Int J Mol Sci. 2016; 17(4):573 [PubMed] Article available free on PMC after 08/07/2017 Related Publications
Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future.

Pivovarcikova K, Peckova K, Martinek P, et al.
"Mucin"-secreting papillary renal cell carcinoma: clinicopathological, immunohistochemical, and molecular genetic analysis of seven cases.
Virchows Arch. 2016; 469(1):71-80 [PubMed] Related Publications
Mucin and mucin-like material are features of mucinous tubular and spindle renal cell carcinoma (MTS RCC) but are rarely seen in papillary renal cell carcinoma (PRCC). We reviewed 1311 PRCC and identified 7 tumors containing extracellular and/or intracellular mucinous/mucin-like material (labeled as PRCCM). We analyzed these using morphological, histochemical, immunohistochemical, and molecular genetic methods (arrayCGH, FISH). Clinical data were available for six of the seven patients (five males and one female, age range 61-78 years). Follow-up was available for four patients (2-4 years); one patient died of widespread metastases. Tumor size ranged from 3 to 5 cm (mean 3.8). Of all cases, histological architecture showed a predominantly papillary pattern. Mucin or mucin-like was extracellular in one, intracellular in three, and both intra/extracellular in three cases. All tumors were positive for AMACR, vimentin, and OSCAR, while CK7 was positive in four. Mucicarmine stain was positive in all cases, PAS in six and Alcian blue in three cases. Five tumors were positive for MUC 1, but none were positive for MUC 2, MUC 4, or MUC 6. In only four cases, genetic analysis could be performed. Gain of chromosomes 7 and 17 was found in two cases; gain of 17 only was found in one case. Loss of heterozygosity of 3p was found in one case together with polysomy of chromosomes 7 and 17. No abnormalities of VHL, fumarate dehydrogenase, and TFE3 genes were detected. We conclude that PRCCM is a rare but challenging subtype of RCC that deserves to be further studied. In all the tumors, the mucin-like material was found in those stained with mucicarmin, but other conventional and immunohistochemical stains did not reveal consistent features of a single mucin. The molecular-genetic profile of these tumors was most consistent with that of typical papillary RCC, although one case had mixed genetic features of papillary and clear RCC. PRCCM has metastatic potential, as evidenced by one case with widespread metastases. It remains to be determined whether PRCCM represents a unique tumor subtype, deserving to be distinguished from other subtypes of PRCC.

Ricketts CJ, Crooks DR, Sourbier C, et al.
SnapShot: Renal Cell Carcinoma.
Cancer Cell. 2016; 29(4):610-610.e1 [PubMed] Related Publications
Renal cell carcinoma (RCC) is a heterogeneous disease made up of a number of different cancer types, with distinct histologies, clinical courses, therapeutic responses, and genetic drivers. Germline mutations in 14 genes have been associated with increased risk of RCC and can result in HIF pathway activation, chromatin dysregulation, and altered metabolism. Knowledge of these pathway alterations can inform the development of targeted therapeutic approaches. To view this SnapShot, open or download the PDF.

Gigante M, Pontrelli P, Herr W, et al.
miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction.
J Transl Med. 2016; 14:84 [PubMed] Article available free on PMC after 08/07/2017 Related Publications
BACKGROUND: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells.
METHODS: We investigated gene expression profiles of tumor-reactive CD8(+) T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8(+) T cells from 25 RCC patients compared to 15 healthy volunteers.
RESULTS: We observed that CD8(+) T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation-associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8(+) T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8(+) T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro.
CONCLUSIONS: Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8(+) T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo.

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Cite this page: Cotterill SJ. Kidney Cancer, Cancer Genetics Web: http://www.cancer-genetics.org/X210201.htm Accessed:

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