Esophageal 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 (134)

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
TP53 17p13.1 P53, BCC7, LFS1, TRP53 -TP53 and Esophageal Cancer
378
EGFR 7p12 ERBB, HER1, mENA, ERBB1, PIG61, NISBD2 Amplification
Overexpression
Prognostic
-EGFR Amplification in Esophageal Cancer
103
ALDH2 12q24.2 ALDM, ALDHI, ALDH-E2 -ALDH2 and Esophageal Cancer
86
PTGS2 1q25.2-q25.3 COX2, COX-2, PHS-2, PGG/HS, PGHS-2, hCox-2, GRIPGHS Overexpression
-PTGS2 (COX2) Overexpression in Esophageal Cancer
-COX2 Polymorphisms and Esophageal Cancer
72
MET 7q31 HGFR, AUTS9, RCCP2, c-Met -C-MET and Esophageal Cancer
46
CDKN1A 6p21.2 P21, CIP1, SDI1, WAF1, CAP20, CDKN1, MDA-6, p21CIP1 -CDKN1A Expression in Esophageal Cancer
41
CD9 12p13.3 MIC3, MRP-1, BTCC-1, DRAP-27, TSPAN29, TSPAN-29 -CD9 expression in Esophageal Cancer
39
ADH1B 4q23 ADH2, HEL-S-117 -ADH1B and Esophageal Cancer
31
ERCC2 19q13.3 EM9, TTD, XPD, TTD1, COFS2, TFIIH -ERCC2 and Esophageal Cancer
29
PIK3CA 3q26.3 MCM, CWS5, MCAP, PI3K, CLOVE, MCMTC, p110-alpha Prognostic
-PIK3CA and Esophogeal Cancer
27
PLCE1 10q23 PLCE, PPLC, NPHS3 -PLCE1 and Esophageal Cancer
24
FGF4 11q13.3 HST, KFGF, HST-1, HSTF1, K-FGF, HBGF-4 -FGF4 and Esophageal Cancer
14
CTTN 11q13.3 EMS1 Amplification
Overexpression
-CTTN and Esophogeal Cancer
13
NOTCH1 9q34.3 hN1, AOS5, TAN1, AOVD1 -NOTCH1 and Esophageal Cancer
13
COL4A5 Xq22 ATS, ASLN, CA54 -COL4A5 and Esophageal Cancer
10
RB1 13q14.2 RB, pRb, OSRC, pp110, p105-Rb, PPP1R130 -RB1 and Esophageal Cancer
10
CYP2A6 19q13.2 CPA6, CYP2A, CYP2A3, P450PB, CYPIIA6, P450C2A -CYP2A6 and Esophageal Cancer
9
SOX2 3q26.3-q27 ANOP3, MCOPS3 -SOX2 and Esoghogeal Cancer
9
CRP 1q23.2 PTX1 -CRP and Esophageal Cancer
8
COL4A6 Xq22 DFNX6, DELXq22.3, CXDELq22.3 -COL4A6 and Esophageal Cancer
8
SPARC 5q31.3-q32 ON -SPARC and Esophageal Cancer
8
CDC25B 20p13 -CDC25B and Esophageal Cancer
8
FSCN1 7p22 HSN, SNL, p55, FAN1 -FSCN1 and Esophageal Cancer
8
CYR61 1p22.3 CCN1, GIG1, IGFBP10 -CYR61 and Esophageal Cancer
7
NFE2L2 2q31 NRF2 -NFE2L2 mutations in Esophageal Cancer
7
ADH1C 4q23 ADH3 -ADH1C and Esophageal Cancer
7
SPRR1A 1q21-q22 SPRK -SPRR1A and Esophageal Cancer
7
SPRR2A 1q21-q22 -SPRR2A and Esophageal Cancer
7
C2orf40 2q12.2 ECRG4 -C2orf40 and Esophageal Cancer
7
HOTAIR 12q13.13 HOXAS, HOXC-AS4, HOXC11-AS1, NCRNA00072 -HOTAIR and Esophageal Cancer
6
DEC1 9q32 CTS9 -DEC1 and Esophageal Cancer
6
SPRR2C 1q21-q22 -SPRR2C and Esophageal Cancer
6
SPRR2B 1q21-q22 -SPRR2B and Esophageal Cancer
6
SPRR1B 1q21-q22 SPRR1, GADD33, CORNIFIN -SPRR1B and Esophageal Cancer
6
S100A9 1q21 MIF, NIF, P14, CAGB, CFAG, CGLB, L1AG, LIAG, MRP14, 60B8AG, MAC387 -S100A9 and Esophageal Cancer
6
STMN1 1p36.11 Lag, SMN, OP18, PP17, PP19, PR22, LAP18, C1orf215 -STMN1 and Esophageal Cancer
6
LOXL2 8p21.3 LOR2, WS9-14 -LOXL2 and Esophageal Cancer
5
EP300 22q13.2 p300, KAT3B, RSTS2 Prognostic
-EP300 and Esophageal Cancer
5
CTSB 8p22 APPS, CPSB -CTSB and Esophageal Cancer
5
S100A2 1q21 CAN19, S100L -S100A2 and Esophageal Cancer
5
UCHL1 4p14 NDGOA, PARK5, PGP95, PGP9.5, Uch-L1, HEL-117, PGP 9.5 -UCHL1 and Esophageal Cancer
5
TNFRSF6B 20q13.3 M68, TR6, DCR3, M68E, DJ583P15.1.1 -TNFRSF6B and Esophageal Cancer
5
MMP7 11q22.2 MMP-7, MPSL1, PUMP-1 -MMP7 Expression in Esophageal Cancer
5
S100A8 1q21 P8, MIF, NIF, CAGA, CFAG, CGLA, L1Ag, MRP8, CP-10, MA387, 60B8AG -S100A8 and Esophageal Cancer
5
MIRLET7C 21q21.1 LET7C, let-7c, MIRNLET7C, hsa-let-7c -MicroRNA let-7c and Esophageal Cancer
5
RRM2B 8q23.1 P53R2, MTDPS8A, MTDPS8B -RRM2B and Esophageal Cancer
5
MMP11 22q11.23 ST3, SL-3, STMY3 -MMP11 and Esophageal Cancer
5
SKIL 3q26 SNO, SnoA, SnoI, SnoN -SKIL and Esophageal Cancer
5
TMEFF2 2q32.3 TR, HPP1, TPEF, TR-2, TENB2, CT120.2 -TMEFF2 and Esophageal Cancer
5
LCN2 9q34 24p3, MSFI, NGAL -LCN2 and Esophageal Cancer
4
RHBDF2 17q25.1 TEC, TOC, TOCG, RHBDL5, RHBDL6, iRhom2 Germline
-RHBDF2 mutations in Tylosis - a familial esophageal cancer syndrome
4
PTPN1 20q13.1-q13.2 PTP1B -PTPN1 and Esophageal Cancer
4
XRCC2 7q36.1 -XRCC2 and Esophageal Cancer
4
PRINS 10p12.1 NCRNA00074 -PRINS and Esophageal Cancer
4
BIRC2 11q22.2 API1, MIHB, HIAP2, RNF48, cIAP1, Hiap-2, c-IAP1 -BIRC2 and Esophageal Cancer
4
GPX3 5q33.1 GPx-P, GSHPx-3, GSHPx-P -GPX3 and Esophageal Cancer
4
HOXA13 7p15.2 HOX1, HOX1J -HOXA13 and Esophageal Cancer
4
TP53INP1 8q22 SIP, Teap, p53DINP1, TP53DINP1, TP53INP1A, TP53INP1B -TP53INP1 and Esophageal Cancer
4
MAPK14 6p21.3-p21.2 RK, p38, CSBP, EXIP, Mxi2, CSBP1, CSBP2, CSPB1, PRKM14, PRKM15, SAPK2A, p38ALPHA -MAPK14 and Esophageal Cancer
4
PTTG1 5q35.1 EAP1, PTTG, HPTTG, TUTR1 -PTTG1 and Esophageal Cancer
4
CKS2 9q22 CKSHS2 -CKS2 and Esophageal Cancer
3
ANO1 11q13.3 DOG1, TAOS2, ORAOV2, TMEM16A -ANO1 and Esophageal Cancer
3
KRT7 12q13.13 K7, CK7, SCL, K2C7 -KRT7 and Esophageal Cancer
3
MT1G 16q13 MT1, MT1K -MT1G and Esophageal Cancer
3
ODC1 2p25 ODC -ODC1 and Esogapheal Cancer
3
NQO2 6p25.2 QR2, DHQV, DIA6, NMOR2 -NQO2 and Esophageal Cancer
3
FGF19 11q13.3 -FGF19 and Esophageal Cancer
3
CLDN3 7q11.23 RVP1, HRVP1, C7orf1, CPE-R2, CPETR2 -CLDN3 and Esophageal Cancer
3
PERP 6q24 THW, KCP1, PIGPC1, KRTCAP1, dJ496H19.1 -PERP and Esophageal Cancer
3
KDM4C 9p24.1 GASC1, JHDM3C, JMJD2C, TDRD14C -KDM4C and Esophageal Cancer
3
CTSL 9q21.33 MEP, CATL, CTSL1 -CTSL1 and Esophageal Cancer
3
ELF3 1q32.2 ERT, ESX, EPR-1, ESE-1 -ELF3 and Esophageal Cancer
3
SOX17 8q11.23 VUR3 -SOX17 and Esophageal Cancer
3
KMT2D 12q13.12 ALR, KMS, MLL2, MLL4, AAD10, KABUK1, TNRC21, CAGL114 -KMT2D and Esophageal Cancer
3
SOX6 11p15.2 SOXD, HSSOX6 -SOX6 and Esophageal Cancer
3
DMBT1 10q26.13 GP340, muclin -DMBT1 supression in Esophageal Cancer?
3
PLA2G4A 1q25 PLA2G4, cPLA2-alpha -PLA2G4A and Esophageal Cancer
3
CREBBP 16p13.3 CBP, RSTS, KAT3A GWS
-CREBBP and Esophageal Cancer
3
TOP2A 17q21-q22 TOP2, TP2A -TOP2A Expression in Esophageal Cancer
3
REG1A 2p12 P19, PSP, PTP, REG, ICRF, PSPS, PSPS1 -REG1A and Esophageal Cancer
2
DRD2 11q23.2 D2R, D2DR -DRD2 and Esophageal Cancer
2
ADAMTS9 3p14.1 -ADAMTS9 and Esophageal Cancer
2
KPNA2 17q24.2 QIP2, RCH1, IPOA1, SRP1alpha -KPNA2 and Esophageal Cancer
2
CD47 3q13.1-q13.2 IAP, OA3, MER6 -CD47 and Esophageal Cancer
2
IFITM1 11p15.5 9-27, CD225, IFI17, LEU13, DSPA2a -IFITM1 and Esophageal Cancer
2
GATA5 20q13.33 GATAS, bB379O24.1 -GATA5 and Esophageal Cancer
2
HHIP 4q28-q32 HIP -HHIP and Esophageal Cancer
2
RAC3 17q25.3 -RAC3 and Esophageal Cancer
2
HLA-E 6p21.3 MHC, QA1, EA1.2, EA2.1, HLA-6.2 -HLA-E and Esophageal Cancer
2
ITGA6 2q31.1 CD49f, VLA-6, ITGA6B -ITGA6 and Esophageal Cancer
2
PINX1 8p23 LPTL, LPTS -PINX1 and Esophageal Cancer
2
CDH3 16q22.1 CDHP, HJMD, PCAD -CDH3 and Esophageal Cancer
2
IRF2 4q34.1-q35.1 IRF-2 -IRF2 and Esophageal Cancer
2
POLK 5q13 DINP, POLQ, DINB1 -POLK and Esophageal Cancer
2
FAT1 4q35 FAT, ME5, CDHF7, CDHR8, hFat1 -FAT1 mutation in Esophogeal Cancer
2
AKR1C2 10p15-p14 DD, DD2, TDD, BABP, DD-2, DDH2, HBAB, HAKRD, MCDR2, SRXY8, DD/BABP, AKR1C-pseudo -AKR1C2 and Esophageal Cancer
2
GPX2 14q24.1 GPRP, GPx-2, GI-GPx, GPRP-2, GPx-GI, GSHPx-2, GSHPX-GI -GPX2 and Esophageal Cancer
2
PTK7 6p21.1-p12.2 CCK4, CCK-4 -PTK7 and Esophageal Cancer
2
PRDX1 1p34.1 PAG, PAGA, PAGB, PRX1, PRXI, MSP23, NKEFA, TDPX2, NKEF-A -PRDX1 and Esophageal Cancer
2
ZNF750 17q25.3 ZFP750 Deletion
-ZNF750 mutation in Esophageal Cancer
2
RARRES1 3q25.32 LXNL, TIG1, PERG-1 -RARRES1 and Esophageal Cancer
2
AQP3 9p13 GIL, AQP-3 -AQP3 and Esophageal Cancer
2
S100A10 1q21 42C, P11, p10, GP11, ANX2L, CAL1L, CLP11, Ca[1], ANX2LG -S100A10 and Esophageal Cancer
2
IL23R 1p31.3 -IL23R and Esophageal Cancer
2
SERPINA1 14q32.1 PI, A1A, AAT, PI1, A1AT, PRO2275, alpha1AT -SERPINA1 and Esophageal Cancer
2
DGCR8 22q11.2 Gy1, pasha, DGCRK6, C22orf12 -DGCR8 and Esophageal Cancer
2
KMT2C 7q36.1 HALR, MLL3 -KMT2C and Esophageal Cancer
2
ASH1L 1q22 ASH1, KMT2H, ASH1L1 -ASH1L and Esophageal Cancer
1
GJB2 13q11-q12 HID, KID, PPK, CX26, DFNA3, DFNB1, NSRD1, DFNA3A, DFNB1A -GJB2 and Esophageal Cancer
1
COX6C 8q22.2 -COX6C and Esophageal Cancer
1
TPM4 19p13.12-p13.11 HEL-S-108 -TPM4 and Esophageal Cancer
1
MAFG 17q25.3 hMAF -MAFG and Esophageal Cancer
1
MIR100 11q24.1 MIRN100, miR-100 -MIR100 and Esophageal Cancer
1
ADAM29 4q34 CT73, svph1 -ADAM29 mutations in Esophageal Cancer
1
S100A3 1q21 S100E -S100A3 and Esophageal Cancer
1
MIR1256 1 MIRN1256, hsa-mir-1256 -MicroRNA miR-1256 and Esophageal Cancer
1
FNBP1 9q34 FBP17 -FNBP1 and Esophageal Cancer
1
PDE4DIP 1q12 MMGL, CMYA2 -PDE4DIP and Esophageal Cancer
1
RASSF10 11p15.3 -RASSF10 and Esophageal Cancer
1
FEZ1 11q24.2 -FEZ1 and Esophageal Cancer
1
NEURL1 10q25.1 neu, NEUR1, NEURL, RNF67, neu-1, bA416N2.1 -NEURL and Esophageal Cancer
1
PLCD1 3p22-p21.3 NDNC3, PLC-III -PLCD1 and Esophageal Cancer
1
NEMF 14q22 NY-CO-1, SDCCAG1 -NEMF and Esophageal Cancer
1
CSTB 21q22.3 PME, ULD, CST6, EPM1, STFB, EPM1A -CSTB and Esophageal Cancer
1
FAT2 5q33.1 CDHF8, CDHR9, HFAT2, MEGF1 -FAT2 mutation in Esophogeal Cancer
1
EZR 6q25.3 CVL, CVIL, VIL2, HEL-S-105 -EZR and Esophageal Cancer
1
SEPT5 22q11.21 H5, CDCREL, PNUTL1, CDCREL1, CDCREL-1, HCDCREL-1 -SEPT5 and Esophageal Cancer
1
PRRX1 1q24 PMX1, PRX1, AGOTC, PHOX1, PRX-1 -PRRX1 and Esophageal Cancer
1
SETD1B 12q24.31 KMT2G, Set1B GWS
-SETD1B and Esophageal Cancer
1
COPS6 7q22.1 CSN6, MOV34-34KD -COPS6 and Esophageal Cancer
1
FTL 19q13.33 LFTD, NBIA3 -FTL and Esophageal Cancer
1
SEPP1 5q31 SeP, SELP, SEPP -SEPP1 and Esophageal Cancer
1
TNFRSF14 1p36.32 TR2, ATAR, HVEA, HVEM, CD270, LIGHTR -TNFRSF14 and Esophageal Cancer
1
PDGFRL 8p22-p21.3 PDGRL, PRLTS -PDGFRL and Esophageal Cancer
1

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

Latest Publications

Chen X, Hu H, Liu J, et al.
FOXF2 promoter methylation is associated with prognosis in esophageal squamous cell carcinoma.
Tumour Biol. 2017; 39(2):1010428317692230 [PubMed] Related Publications
Esophageal squamous cell carcinoma is a commonly malignant tumor of digestive tract with poor prognosis. Previous studies suggested that forkhead box F2 ( FOXF2) could be a candidate gene for assessing and predicting the prognosis of human cancers. However, the relationship between FOXF2 promoter methylation and the prognosis of esophageal squamous cell carcinoma remained unclear. Formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma tissues of 135 esophageal squamous cell carcinoma patients were detected for FOXF2 promoter methylation status by methylation-specific polymerase chain reaction approach. DNA methylation results were evaluated with regard to clinicopathological features and overall survival. Our study confirmed that FOXF2 promoter hypermethylation could independently predict a poorer overall survival of esophageal squamous cell carcinoma patients ( p = 0.002), which was consistent with the data mining results of the data from 82 esophageal squamous cell carcinoma patients in The Cancer Genome Atlas datasets ( p = 0.036). In addition, no correlation was found between FOXF2 promoter methylation and other clinic pathological parameters (age, gender, differentiation, lymph node metastasis, stage, cutting edge, vascular invasion, smoking behavior, and drinking history). In conclusion, FOXF2 methylation might be a useful prognostic biomarker for esophageal squamous cell carcinoma patients.

Vrana D, Matzenauer M, Aujesky R, et al.
Potential Predictive Role of MicroRNAs in the Neoadjuvant Treatment of Esophageal Cancer.
Anticancer Res. 2017; 37(2):403-412 [PubMed] Related Publications
Esophageal cancer is a disease with disappointing prognosis. Currently, there are no predictive factors that can identify patients who on the one hand would likely benefit from tri-modality management and, on the other hand, would not be significantly affected by the morbidity accompanying the treatment. MicroRNAs are short non-coding RNAs responsible for post-transcriptional modification of gene expression by binding to 3'-UTR of messenger RNA and represent emerging potential predictive biomarkers of treatment (chemotherapy and radiotherapy) efficacy and toxicity. We reviewed the current literature, addressing the potential predictive role of microRNAs for efficacy of chemotherapy (specifically cisplatin, 5-fluorouracil, doxorubicin and paclitaxel) and radiotherapy, including predicted targets in the cell. Altogether 82 articles were identified and included in this review. This may be the first review on this topic specifically focusing on neoadjuvant treatment of esophageal cancer.

Bhat AA, Wani HA, Ishaq S, et al.
Promoter Hypermethylation and Its Impact on Expression of MGMT Gene in the GIT Malignant Patients of Kashmiri Origin.
Cancer Invest. 2017; 35(2):116-121 [PubMed] Related Publications
Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Gastrointestinal tract (GIT) cancer is a major medical and economic burden worldwide. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumor suppressor genes. Although a number of cancer-associated genes have been found to be hypermethylated in GIT cancer, valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. O6-methyguanine DNA methyltransferase (MGMT) is a DNA-repair gene that removes mutagenic and cytotoxic adducts from the O6 position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression have been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human GIT carcinomas. A total of 210 GIT tumor samples and 90 adjacent normal tissues were analyzed for MGMT promoter methylation by methylation-specific polymerase chain reaction after bisulfite modification of DNA and same samples were analyzed for MGMT protein expression by Western blotting. The methylation frequencies of MGMT gene promoter were 41.4%, 34.2%, and 44.2% in stomach, esophageal, and colorectal cancer cases while as 16.6, 13.3, and 13.3 in respective controls. MGMT protein was found downregulated in controls of all GIT. The results suggest that methylation at CpG islands of MGMT may be responsible for the downregulation of MGMT protein expression in GIT cancers.

Fendereski M, Zia MF, Shafiee M, et al.
MicroRNA-196a as a Potential Diagnostic Biomarker for Esophageal Squamous Cell Carcinoma.
Cancer Invest. 2017; 35(2):78-84 [PubMed] Related Publications
We observed significant up-regulation of miR-196a in esophageal squamous cell carcinoma (ESCC) as compared with their adjacent normal tissue (p = .002). Receiver operating characteristics curve analysis confirmed the suitability of miR-196a as a potential tumor marker for diagnosis of ESCC. Furthermore, analysis of miR-196a levels in saliva samples determined an average of 27-fold up-regulations in ESCC patients compared with healthy group. Our results suggest that salivary miR-196a may be a suitable noninvasive biomarker for diagnosis of ESCC. In addition, molecular pathway enrichment analysis of microRNA (miR)-196a determined focal adhesion, spliceosome and p53 signaling pathways as the most relevant pathways with miR-196a targetome.

Bartley AN, Washington MK, Ventura CB, et al.
HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology.
Am J Clin Pathol. 2016; 146(6):647-669 [PubMed] Related Publications
CONTEXT: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA.
OBJECTIVES: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making.
DESIGN: The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA.
RESULTS: The panel is proposing 11 recommendations with strong agreement from the open-comment participants.
RECOMMENDATIONS: The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance.
CONCLUSIONS: This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.

Chen P, Shan Z, Zhao J, et al.
NFAT1 promotes cell motility through MMP-3 in esophageal squamous cell carcinoma.
Biomed Pharmacother. 2017; 86:541-546 [PubMed] Related Publications
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors and the prognosis of patients remains poor. Increasing evidence suggests that nuclear factor of activated T cell (NFAT1) plays an important role in the development and progression of cancers. Herein, we show that NFAT1 was overexpressed in human ESCC, which was significantly associated with advanced tumor stage and lymph node metastasis. Functional studies found that NFAT1 silencing could suppress cell migration and invasion through MMP-3. The data therefore suggest that NFAT1 plays an important adverse role in the development and progression of ESCC, implicating possible application in clinics as a biomarker and a potential new therapeutic target.

Imai T, Oue N, Sentani K, et al.
KIF11 Is Required for Spheroid Formation by Oesophageal and Colorectal Cancer Cells.
Anticancer Res. 2017; 37(1):47-55 [PubMed] Related Publications
BACKGROUND: Oesophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC) are common types of human cancer. Spheroid colony formation is used to characterize cancer stem cell (CSCs). In the present study, we analyzed the significance of kinesin family 11 (KIF11 in human ESCC and CRC.
MATERIALS AND METHODS: Expression of KIF11 in 105 ESCC and 100 CRC cases was determined using immunohistochemistry. RNA interference was used to inhibit KIF11 expression in ESCC and CRC cell lines.
RESULTS: In total, 61 out of 105 (58%) ESCC and 62 out of 100 (62%) CRC cases were positive for KIF11. Expression of KIF11 was not associated with any clinicopathological characteristics. Both the number and size of spheres produced by from TE-5 ESCC cells and DLD-1 CRC cells were significantly reduced upon KIF11 siRNA transfection compared to negative control siRNA transfection.
CONCLUSION: These results indicate that KIF11 plays an important role in CSCs of ESCC and CRC.

Zhang H, Zhao JH, Suo ZM
Knockdown of HOXA5 inhibits the tumorigenesis in esophageal squamous cell cancer.
Biomed Pharmacother. 2017; 86:149-154 [PubMed] Related Publications
Homeobox A5 (HOXA5) is a member of the homeobox (HOX) family and was upregulated in many types of tumors. However, its expression and role in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, the aim of this study was to investigate the expression and function of HOXA5 in ESCC. Our results showed that HOXA5 was highly expressed in ESCC cell lines. The in vitro experiments demonstrated that knockdown of HOXA5 significantly inhibited the proliferation, migration and invasion of ESCC cells. Furthermore, the in vivo experiments showed that knockdown of HOXA5 significantly inhibited the tumor growth of ESCC in mice xenograft model. Finally, sh-HOXA5 inhibited the expression of β-catenin, cyclin D1 and c-Myc in ESCC cells. Taken together, these data revealed that knockdown of HOXA5 suppressed the proliferation and metastasis partly by interfering with Wnt/β-catenin signaling pathway in ESCC cells. Therefore, these findings suggest that HOXA5 may be a potential therapeutic target for the treatment of ESCC.

Kwak EL, Hong TS, Forcione DG, et al.
Case 35-2016. A 62-Year-Old Man with Dysphagia.
N Engl J Med. 2016; 375(20):1983-1991 [PubMed] Related Publications

Yu J, Wang R, Wu J, et al.
Knockdown of Minichromosome Maintenance Proteins Inhibits Foci Forming of Mediator of DNA-Damage Checkpoint 1 in Response to DNA Damage in Human Esophageal Squamous Cell Carcinoma TE-1 Cells.
Biochemistry (Mosc). 2016; 81(10):1221-1228 [PubMed] Related Publications
Esophageal squamous cell carcinoma (ESCC) has a high morbidity in China and its treatment depends greatly on adjuvant chemotherapy. However, DNA damage repair in cancer cells severely affects the outcome of treatment. This study investigated the potential mechanism regarding mediator of DNA-damage checkpoint 1 (MDC1) and minichromosome maintenance proteins (MCMs) during DNA damage in ESCC. Recombinant vectors of MDC1 and MCMs with tags were constructed and transfected into human ESCC cell line TE-1. Immunoprecipitation and mass spectrometry were performed to screen the MCMs interacting with MDC1, and direct interaction was confirmed by glutathione S-transferase (GST) pull-down assay in vitro. MCM2 and MCM6 were knocked down by shRNAs, after which chromatin fraction and foci forming of MDC1 upon bleomycin-induced DNA damage were examined. The results showed that MCM2/3/5/6 were immunoprecipitated by antibodies against the tag of MDC1 in TE-1 nuclei, and the GST pull-down assay indicated the direct interaction. Knockdown of MCM2 or MCM6 reduced the chromatin fraction of MDC1 according to Western blot results. Moreover, knockdown of MCM2 or MCM6 could significantly inhibit foci forming of MDC1 in TE-1 nuclei in response to bleomycin-induced DNA damage (p < 0.001). This study indicates the direct interaction between MDC1 and MCMs in TE-1 nuclei. Downregulation of MCMs can inhibit chromatin fraction and foci forming of MDC1 in TE-1 cells upon DNA damage, which suggests MCMs and MDC1 as potential targets to improve the outcome of chemotherapy in ESCC.

Ren K, Zhang W, Wu G, et al.
Synergistic anti-cancer effects of galangin and berberine through apoptosis induction and proliferation inhibition in oesophageal carcinoma cells.
Biomed Pharmacother. 2016; 84:1748-1759 [PubMed] Related Publications
Galangin is an active pharmacological ingredient from propolis and Alpinia officinarum Hance, and has been reported to have anti-cancer and antioxidative properties. Berberine, a major component of Berberis vulgaris extract, exhibits potent anti-cancer activities through distinct molecular mechanisms. However, the anticancer effect of galangin in combination with berberine is still unknown. In the present study, we demonstrated that the combination of galangin with berberine synergistically resulted in cell growth inhibition, apoptosis and cell cycle arrest at G2/M phase with the increased intracellular reactive oxygen species (ROS) levels in oesophageal carcinoma cells. Pretreatment with ROS scavenger promoted the apoptosis dramatically induced by co-treatment with galangin and berberine. Treatment with galangin and berberine alone caused the decreased expressions of Wnt3a and β-catenin. Interestingly, combination of galangin with berberine could further suppress Wnt3a and β-catenin expression and induce apoptosis in cancer cells. Additionally, in nude mice with xenograft tumors, the combinational treatment of galangin and berberine significantly inhibited the tumor growth without obvious toxicity. Overall, galangin in combination with berberine presented outstanding synergistic anticancer role in vitro and in vivo, indicating that the beneficial combination of galangin and berberine might provide a promising treatment for patients with oesophageal carcinoma.

Hu HB, Jie HY, Zheng XX
Three Circulating LncRNA Predict Early Progress of Esophageal Squamous Cell Carcinoma.
Cell Physiol Biochem. 2016; 40(1-2):117-125 [PubMed] Related Publications
BACKGROUND/AIMS: Previous studies revealed that circulating (either from plasma or serum) long non-coding RNA may predict the occurrence or prognosis of multiple human malignant tumors. In this study, we mainly explored whether circulating lncRNAs can be utilized as biomarkers predicting the development of human esophageal squamous cell carcinoma (ESCC).
METHODS: LncRNA microarray was applied to screen the potential biomarkers for ESCC. Each group contained three individual plasma samples. A multi-stage validation and risk score formula detection were used for validation.
RESULTS: Eleven dysregulated lncRNAs were obtained after Venny analysis. Further validation in a larger cohort including 205 ESCC patients, 82 patients suffering from esophagus dysplasia and 210 healthy controls confirmed that increased Linc00152, CFLAR-AS1 and POU3F3 might be potential biomarkers for predicting the early progress with an area under curve (AUC) of 0.698, 0.651 and 0.584, respectively. The merged AUC of the three factors and merged with CEA was 0.765 and 0.955, respectively. We also revealed that circulating levels of three lncRNAs were associated with poor post-surgery prognosis of ESCC patients.
CONCLUSIONS: The three circulating lncRNAs might serve as potential biomarkers for predicting the early occurrence of ESCC.

Bartley AN, Washington MK, Ventura CB, et al.
HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology.
Arch Pathol Lab Med. 2016; 140(12):1345-1363 [PubMed] Related Publications
CONTEXT: - ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA.
OBJECTIVES: - To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making.
DESIGN: - The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA.
RESULTS: - The panel is proposing 11 recommendations with strong agreement from the open-comment participants.
RECOMMENDATIONS: - The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance.
CONCLUSIONS: - This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.

Song W, Zou SB
Prognostic role of lncRNA HOTAIR in esophageal squamous cell carcinoma.
Clin Chim Acta. 2016; 463:169-173 [PubMed] Related Publications
BACKGROUND: HOX transcript antisense intergenic RNA (HOTAIR) may be implicated in cancer development and progression. Clinical studies have suggested that HOTAIR may be related to poor prognosis in esophageal squamous cell carcinoma (ESCC). This study was designed to clarify the prognostic role of HOTAIR in ESCC.
METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure (CNKI) databases were searched to identify studies evaluating the prognostic significance of HOTAIR in ESCC. Pooled hazard ratios (HRs) for overall survival (OS), lymph node metastasis (LNM), and cancer stage were calculated using fixed-effects/random-effects models.
RESULTS: A total of 510 patients from five studies were included. Meta-analysis revealed that high HOTAIR expression was significantly correlated with poor OS (HR, 2.37; 95% CI, 1.80-3.11; P<0.00001) and positive LNM (RR, 1.96; 95% CI, 1.07-3.60; P=0.03).
CONCLUSION: Elevated lncRNA HOTAIR indicated a poor prognosis for patients with ESCC, and it may also have predictive potential for ESCC metastasis.

Song JH, Han YM, Kim WH, et al.
Oxidative stress from reflux esophagitis to esophageal cancer: the alleviation with antioxidants.
Free Radic Res. 2016; 50(10):1071-1079 [PubMed] Related Publications
The incidence of reflux esophagitis increases in world, affecting approximately 20% of Western populations and its consequent lesion, Barrett's esophagus (BE), established as the primary precursor lesion of esophageal adenocarcinoma (EAC) or Barrett associated adenocarcinoma (BAA), is also increasing in incidence in Asian countries as well as Western countries. The fact that surveillance strategies have not had a major benefit in decreasing the incidence of EAC increased attention to arrest or delay the progression of BE to EAC. Since sustained inflammation and consequent oxidative stress plays core pathogenic role in reflux esophagitis, BE, and BAA, attention paid to anti-inflammatory and antioxidative agents in the treatment of reflux esophagitis. Since the risk of esophagitis is associated with hiatal hernia, body mass index, and duodenogastric reflux, and acid exposure, lifestyle modification and agents to control gastric acidity might be mainstay for treatment, but several studies consistently showed the implication of robust oxidative stress in reflux associated esophageal diseases. In this review article, the pathogenic implication of oxidative stress will be introduced in the development of reflux esophagitis, BE, and EAC. Also, since there is great interest in complete healing of reflux esophagitis and chemoprevention to prevent or slow malignant transformation, the contribution of antioxidants or antioxidative agents, which was delivered during SFRR-Asia 2015 (Chiangmai, Thailand), will be described. Also, the molecular mechanisms how the antioxidative drugs, rebamipide, ecabet sodium, and pantoprazole exerted significant protection from acids or bile acids-associated esophagitis are included.

Liu W, Dong Z, Liang J, et al.
Downregulation of Potential Tumor Suppressor miR-203a by Promoter Methylation Contributes to the Invasiveness of Gastric Cardia Adenocarcinoma.
Cancer Invest. 2016; 34(10):506-516 [PubMed] Related Publications
Like many tumor suppressor genes, some miRNA genes harboring CpG islands undergo methylation-mediated silencing. In the study, we found significant downregulation and proximal promoter methylation of miR-203a and miR-203b in gastric cardia adenocarcinoma (GCA) tissues. The methylation status of miR-203a and miR-203b in tumor tissues was negatively correlated with their expression level. GCA patients in stage III and IV with reduced expression or hypermethylation of miR-203a demonstrated poor patient survival. In all, miR-203a and miR-203b may function as tumor suppressive miRNAs, and reactivation of miR-203a may have therapeutic potential and may be used as prognostic marker for GCA patients.

Ohshima Y, Kaira K, Yamaguchi A, et al.
Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma.
Cancer Sci. 2016; 107(10):1499-1505 [PubMed] Free Access to Full Article Related Publications
System l amino acid transporter 1 (LAT1) is highly expressed in various types of human cancer, and contributes to cancer growth and survival. Recently, we have shown that LAT1 expression is closely related to the growth and aggressiveness of esophageal cancer, and is an independent marker of poor prognosis. However, it remains unclear whether LAT1 inhibition could suppress esophageal cancer growth. In this study, we investigated the tumor-suppressive effects of the inhibition of LAT1. Both LAT1 and CD98, which covalently associates to LAT1 on the membrane, were expressed in human esophageal cancer cell lines KYSE30 and KYSE150. Quantitative PCR analysis showed that the expression of LAT1 was much higher than other subtypes of LAT. A selective inhibitor of LAT, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), suppressed cellular uptake of l-(14) C-leucine and cell proliferation in a dose-dependent manner. It also suppressed phosphorylation of mammalian target of rapamycin, 4E-BP1, and p70S6K protein, and induced cell cycle arrest at G1 phase. These results suggest that suppression of both mammalian target of rapamycin signaling and cell cycle progression is involved in BCH-induced growth inhibition. In tumor-bearing mice, daily treatment with BCH significantly delayed tumor growth and decreased glucose metabolism, indicating that LAT1 inhibition potentially suppresses esophageal cancer growth in vivo. Thus, our results suggest that LAT1 inhibition could be a promising molecular target for the esophageal cancer therapy.

Song C, Lu P, Shi W, et al.
MiR-622 functions as a tumor suppressor and directly targets E2F1 in human esophageal squamous cell carcinoma.
Biomed Pharmacother. 2016; 83:843-849 [PubMed] Related Publications
PURPOSE: MicroRNA-622 has been proven down-regulated in many human malignancies and correlated with tumor progression. However, its role in esophageal squamous cell carcinoma (ESCC) is still unclear. The aim of this study was to explore the expression and function of miR-622 in ESCC.
METHODS: Using quantitative RT-PCR, we detected miR-622 expression in ESCC cell lines and primary tumor tissues. The association of miR-622 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-622 on the biological behavior of ESCC cells were investigated. At last, the potential regulatory function of miR-622 on E2F1 expression was confirmed.
RESULTS: miR-622 was found to be down-regulated in ESCC tissues and cell lines. Decreased miR-622 expression was closely correlated with aggressive clinicopathological features and poor overall survival. Multivariate regression analysis corroborated that low level of miR-622 expression was an independent unfavourable prognostic factor for patients with ESCC. Up-regulation of miR-622 could significantly reduce ESCC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while down-regulation of miR-622 showed opposite effects. Further, E2F1 was confirmed as a direct target of miR-622 by using Luciferase Reporter Assay.
CONCLUSIONS: These findings indicate that miR-622 may act as a tumor suppressor in ESCC and would serve as a potential therapy target for this disease.

Huang C, Yu Z, Yang H, Lin Y
Increased MALAT1 expression predicts poor prognosis in esophageal cancer patients.
Biomed Pharmacother. 2016; 83:8-13 [PubMed] Related Publications
AIM: This study was designed to determine the expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in patients with esophageal cancer (EC). In addition, we attempted to seek the prognostic value of MALAT1 in EC based on its expression.
METHODS: The expression of MALAT1 in EC tissues and cell lines were measured by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). The association between MALAT1 expression and the clinical characteristics was analyzed using Chi-square test. Kaplan-Meier survival curves were plotted to describe the overall survival of EC patients with different expression of MALAT1. Cox regression analysis was per formed to evaluate the prognostic value of MALAT1 for EC patients.
RESULTS: Expression levels of MALAT1 were significantly higher in EC tissues and cells than the controls (P<0.05). MALAT1 expression was tightly related to lymphatic invasion (P=0.018), distant metastasis (P=0.033) and tumor differentiation (P=0.025), but shared no association with age, gender and tumor location (P>0.05). In addition, patients with high MALAT1 expression had a shorter overall survival than those with low MALAT1 (P<0.001). The results of Cox analysis shown that MALAT1 was significantly linked with the prognosis of EC patients (HR=6.638; P=0.000; 95% CI=2.948-14.947).
CONCLUSION: Taken together, the expression of MALAT1 could be a predictor for prognosis of EC patients.

Kilic-Baygutalp N, Ozturk N, Orsal-Ibisoglu E, et al.
Evaluation of serum HGF and CK18 levels in patients with esophageal cancer.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
Cytokeratins are thought to play a role in apoptosis. Cytokeratin 18 (CK18) is involved in the formation of intracellular cytoskeleton, and has been considered a promising apoptosis marker in gastrointestinal carcinomas. Growth factors, including hepatocyte growth factor (HGF), may provide a microenvironment for malignant cells. In this study, we aimed to compare serum HGF and CK18 levels between esophageal squamous cell carcinoma patients and healthy controls. The study included 41 adult patients (20 male, 21 female) diagnosed with esophageal squamous cell carcinoma, with a mean age of 63.54 ± 10.88 years (range, 41-82 years). We also recruited 39 age and gender-matched healthy control subjects. Venous blood samples were taken; serum HGF and CK18 concentrations were determined via ELISA. Results indicated that serum HGF levels were higher in patients (1.37 ± 0.63 ng/mL) as compared to the healthy subjects (0.41 ± 0.29 ng/mL). Similarly, serum CK18 levels were higher in the patient group (2.53 ± 1.33 ng/mL) than in the control group (0.34 ± 0.23 ng/mL) (P < 0.001). In addition, serum HGF and CK18 levels were positively correlated with metastasis stage, tumor stage, and disease stage of esophageal squamous cell carcinoma. To our knowledge, this is the first study to evaluate serum HGF and CK18 levels in patients with esophageal squamous cell carcinoma. The results suggest that serum CK18 and HGF levels may be used as prognostic and disease monitoring biomarkers of esophageal squamous cell carcinoma.

Yu ZS, Song XH, Gan HM, et al.
Activation of Src tyrosine kinase in esophageal carcinoma cells in different regulatory environments and corresponding occurrence mechanism.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
This study aims at observing the expression of activated Src tyrosine kinase in esophageal squamous cell carcinoma (ESCC), and exploring the relationship of Src tyrosine kinase with the occurrence and progression of ESCC. Immunohistochemistry, immunofluorescence, and immunoblotting are employed to investigate the expression of Src tyrosine kinase in the ESCC tissue. Cellular immunofluorescence is used to measure the expression of activated Src tyrosine kinase in TE1 and TE9 cell lines of human ESCC tissues and EPC1-htert and EPC2-htert cell lines of esophageal epithelial cells. Src tyrosine kinase is overexpressed in ESCC tissue and underexpressed in normal esophageal mucosa. Furthermore, it is overexpressed in the TE1 and TE9 cell lines of human ESCC tissue and underexpressed in the EPC1-htert and EPC2-htert cell lines of esophageal epithelial cells. Src tyrosine kinase shows a higher expression in human ESCC tissue than in normal esophageal mucosa. The difference is statistically significant (P < 0.05). The activation of Src tyrosine kinase plays an important role in the occurrence and development of ESCC.

Verbeek RE, Siersema PD, Vleggaar FP, et al.
Toll-like Receptor 2 Signalling and the Lysosomal Machinery in Barrett's Esophagus.
J Gastrointestin Liver Dis. 2016; 25(3):273-82 [PubMed] Related Publications
BACKGROUND AND AIMS: Inflammation plays an important role in the development of esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett's esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation-associated carcinogenesis. We examined the expression of TLR2 in the esophagus and the effect of long-term TLR2 activation on morphological changes and expression of factors involved in lysosomal function in a Barrett's esophagus epithelium cell line.
METHODS: TLR2 expression in normal squamous esophagus, reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma biopsies was assessed with Q-RT-PCR, in situ hybridization and immunohistochemistry. Barrett's esophagus epithelium cells (BAR-T) were incubated with acid and bile salts in the presence or absence of the TLR2 agonist Pam3CSK4 for a period up to 4 weeks. Morphological changes were assessed with electron microscopy, while Q-RT-PCR was used to determine the expression of lysosomal enzymes (Cathepsin B and C) and factors involved in endocytosis (LAMP-1 and M6PR) and autophagy (LC3 and Rab7).
RESULTS: TLR2 was expressed in normal squamous esophagus, reflux esophagitis, Barrett's esophagus but was most prominent in esophageal adenocarcinoma. Long-term TLR2 activation in acid and bile salts exposed BAR-T cells resulted in more and larger lysosomes, more mitochondria and increased expression of LAMP-1, M6PR, Cathepsin B and C when compared to BAR-T cells incubated with acid and bile salts but no TLR2 agonist. Factors associated with autophagy (LC3 and Rab7) expression remained largely unchanged.
CONCLUSION: Activation of TLR2 in acid and bile salts exposed Barrett epithelium cells resulted in an increased number of mitochondria and lysosomes and increased expression of lysosomal enzymes and factors involved in endocytosis.

Cheng L, Yang F, Zhou B, et al.
RAB23, regulated by miR-92b, promotes the progression of esophageal squamous cell carcinoma.
Gene. 2016; 595(1):31-38 [PubMed] Related Publications
RAB23, a member of Ras-related small GTPase family, has been reported to be up-regulated in several cancer types. However, its biological functions and the underlying molecular mechanisms for its oncogenic roles in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we have shown that the expression of RAB23 was elevated in ESCC tissues and ESCC cells. Overexpression of RAB23 promoted the growth and migration of the ESCC cells, while knocking down the expression RAB23 inhibited the growth, migration and metastasis of the ESCC cells. The molecular mechanism study showed that RAB23 activated beta-catenin/TCF signaling and regulated the expression of several target genes. In the further study, it was found that the expression of RAB23 was regulated by the miR-92b. Forced expression of MiR-92b decreased the mRNA and protein level of RAB23, and RAB23 rescued the biological functions of miR-92b. Taken together, this study revealed the oncogenic roles and the regulation of RAB23 in ESCC, suggesting RAB23 might be a therapeutic target.

Jin YY, Chen QJ, Xu K, et al.
Involvement of microRNA-141-3p in 5-fluorouracil and oxaliplatin chemo-resistance in esophageal cancer cells via regulation of PTEN.
Mol Cell Biochem. 2016; 422(1-2):161-170 [PubMed] Related Publications
microRNAs (miRNAs) act as a major regulator of acquired chemo-resistance in various types of cancer therapeutics. This study investigated the contribution of miRNAs in influencing multiple drug resistance in esophageal squamous cell carcinoma (ESCC). The sensitivity of four ESCC cell lines (EC109, EC9706, TE-1 and KYSE-150) to 5-fluorouracil (5-FU) and oxaliplatin (OX) was determined by MTT assay. A 5-FU and OX-resistant subline, EC9706R, was established by continuous exposure to stepwise increasing concentration of 5-FU and OX. Microarray technology was used to compare the differential expression of miRNAs between resistant cells and parental cells. Chemo-sensitivity assay was performed to evaluate drug response in EC9706R cells transfected with miRNA mimic or inhibitor. The direct targets of miRNA were identified by employing pathway analysis and then confirmed with luciferase assay. Sixty ESCC tissue samples and their paired adjacent normal tissues were collected to validate the expression of identified miRNA. Mouse models were further utilized to investigate the function of miRNA on acquired chemo-resistance. MicroRNA panel results indicated that a total of 12 miRNAs were differentially expressed and miR-141-3p was highly over expressed in resistant cells. Inhibition of miR-141-3p reversed acquired chemo-resistance in EC9706R cells by stimulating apoptosis. The expression of miR-141-3p was significantly increased in ESCC tissue samples compared to their matched distant normal tissues. In addition, the elevated miR-141-3p expression was found to be associated with ESCC differentiation status and TNM stage. Moreover, Phosphatase and tensin homolog (PTEN) was identified as direct target of miR-141-3p. Western blot exhibited altered protein levels of PTEN, Akt, and PI3k with miR-141-3p inhibitor. An inverse correlation between PTEN expression and miR-141-3p expression was also observed in tissue samples. EC9706R xenograft mouse model became sensitized to 5-FU and OX treatment following miR-141-3p inhibitor transfection in vivo. Our study demonstrated that miR-141-3p contributed to an acquired chemo-resistance through PTEN modulation both in vitro and in vivo.

Wang F, Wang J, Yang X, et al.
MiR-424-5p participates in esophageal squamous cell carcinoma invasion and metastasis via SMAD7 pathway mediated EMT.
Diagn Pathol. 2016; 11(1):88 [PubMed] Free Access to Full Article Related Publications
BACKGROUNDS: ESCC is a life-threatening disease due to invasion and metastasis in the early stage. Great efforts had been made to detect the molecular mechanisms which led to the invasion and metastasis in ESCC. Recent evidence had suggested that deregulation of miR-424-5p took an important role in cancers. However, its role and functional mechanism in ESCC had seldom been elucidated.
METHODS: The expression levels of miR-424-5p were detected in ESCC tissues and cell lines by real-time PCR methods. Then, the invasion, metastasis and proliferation ability of ESCC cell lines transfected with miR-424-5p mimics were analyzed separately by transwell invasion assay, wound healing assay and cell proliferation assay. Finally, the target gene of miR-424-5p was studied and verified by luciferase activity assay. And the role of miR-424-5p in EMT was also investigated by real-time PCR and western blot assay.
RESULTS: We showed that the expression levels of miR-424-5p were decreased both in ESCC tissues and cell lines. Furthermore, the expression levels of miR-424-5p were negatively linked to lymph node metastasis in ESCC tissues. Restoration of miR-424-5p in EC-1 cells by using miR-424-5p mimics could decrease the invasion, metastasis and proliferation of EC-1 cells, indicating its role in inhibition on the invasion and metastasis ability of ESCC cells and tissues. In addition, we demonstrated that SMAD7 was a specific target gene for miR-424-5p by luciferase activity assay and miR-424-5p could not only negatively regulate SMAD7 expression but also participate in EMT via SMAD7, because overexpression of SMAD7 could partly enhance the miR-424-5p anti-EMT function.
CONCLUSIONS: Our results described that miR-424-5p -SMAD7 pathway contributed to ESCC invasion and metastasis and up-regulation of miR-424-5p perhaps provided a strategy for preventing tumor invasion, metastasis.

Ma Y, Wang B, Guo Y, et al.
Inhibition of miR-196a affects esophageal cancer cell growth in vitro.
Biomed Pharmacother. 2016; 84:22-27 [PubMed] Related Publications
Esophageal cancer (EC) is one of the most common causes of cancer-related mortality worldwide. Several oncogenes such as miR-196a have been implicated in the carcinogenesis and progression of EC. The purpose of this study was to determine the effects of anti-miR-196a on the growth and survival of human EC cells in vitro. We found that miR-196a was highly expressed in both TE1 and EC109 cells and that miR-196a knockdown inhibited cell proliferation and migration. Furthermore, miR-196a knockdown sensitized EC cells to radiation treatment and chemotherapy. Inhibition of miR-196a also altered cell cycle progression and induced G2/M arrest, which was related to changes in the levels of cyclin B1. ABCG2, which was highly expressed in untransfected EC cells, was inhibited by miR-196a knockdown. Thus, our results confirm the fact that miR-196a is highly involved in the biological behavior of EC progression in vitro. We conclude that miR-196a is a useful biological marker and potential therapeutic target for the clinical treatment of human EC.

Lu Q, Xu L, Li C, et al.
miR-214 inhibits invasion and migration via downregulating GALNT7 in esophageal squamous cell cancer.
Tumour Biol. 2016; 37(11):14605-14614 [PubMed] Related Publications
Previous studies verified that miR-214 is of great significance in the invasion and migration of a variety of cancers. It has been demonstrated that UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) is a putative target of miR-214. We performed this study to figure out how miR-214 and GALNT7 play their roles in the invasion and migration of esophageal squamous cell carcinoma (ESCC). The expression of miR-214 was significantly downregulated in tumors compared to the corresponding non-tumor tissues while GALNT7 showed an opposite tendency. The low expression of miR-214 and the high expression of GALNT7 were found positively correlated with poor tumor differentiation (P = 0.004), tumor invasion (P = 0.013), and lymph node metastasis (P = 0.012) in ESCC patients. Functional study demonstrated that overexpression of miR-214 or knockdown of GALNT7 could weaken invasive and migratory ability in Eca109, TE1, and KYSE150. Moreover, tumorigenicity assay showed us mice injected with cells containing miR-214 mimic or GALNT7 small interfering RNA formed substantially smaller tumors than that in miR-214 inhibitor group. Consequently, we concluded that miR-214 shows potential to be a diagnostic marker and therapeutic target in ESCC.

Dai F, Liu T, Zheng S, et al.
MiR-106b promotes migration and invasion through enhancing EMT via downregulation of Smad 7 in Kazakh's esophageal squamous cell carcinoma.
Tumour Biol. 2016; 37(11):14595-14604 [PubMed] Related Publications
Accumulated evidence suggests that miR-106b played a key role in the promotion of the metastases of cancer; however, little is known about miR-106b in esophageal squamous cell carcinoma (ESCC). To investigate expression level of miR-106b in ESCC tissues, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-106b expression in 35 Kazakh's ESCC and paired normal adjacent tissues (NATs). To evaluate the role mediated by miR-106b in the proliferation, migration, and invasion, MTT, wound healing, and transwell assays were employed, respectively. Luciferase reporter assay was used to identify the downstream target through miR-106b. To understand the regulation between miR-106b and Smad 7, qRT-PCR and western blot were performed. The present study showed that miR-106b was pronouncedly upregulated in ESCC relative to paired NAT and that upregulated miR-106b was significantly associated with lymph node metastases. MiR-106b was found to be able to promote proliferation, migration, and invasion of ESCC cells in vitro. Smad 7 was confirmed as a downstream target of miR-106b in our experimental setting. Smad 7 was remarkably downregulated in ESCC compared with paired NAT. In addition, upregulation of miR-106b can promote epithelial mesenchymal transition (EMT) in ESCC cell in vitro. Our results indicated that miR-106b can promote migration and invasion of ESCC cells through enhancing EMT process via downregulation of Smad 7, suggesting that miR-106b can be a potential molecular phenotype in ESCC metastases.

Haque MH, Gopalan V, Yadav S, et al.
Detection of regional DNA methylation using DNA-graphene affinity interactions.
Biosens Bioelectron. 2017; 87:615-621 [PubMed] Related Publications
We report a new method for the detection of regional DNA methylation using base-dependent affinity interaction (i.e., adsorption) of DNA with graphene. Due to the strongest adsorption affinity of guanine bases towards graphene, bisulfite-treated guanine-enriched methylated DNA leads to a larger amount of the adsorbed DNA on the graphene-modified electrodes in comparison to the adenine-enriched unmethylated DNA. The level of the methylation is quantified by monitoring the differential pulse voltammetric current as a function of the adsorbed DNA. The assay is sensitive to distinguish methylated and unmethylated DNA sequences at single CpG resolution by differentiating changes in DNA methylation as low as 5%. Furthermore, this method has been used to detect methylation levels in a collection of DNA samples taken from oesophageal cancer tissues.

Wang Y, Wang S, Shen J, et al.
Genotype Distribution of Human Papillomavirus among Women with Cervical Cytological Abnormalities or Invasive Squamous Cell Carcinoma in a High-Incidence Area of Esophageal Carcinoma in China.
Biomed Res Int. 2016; 2016:1256384 [PubMed] Free Access to Full Article Related Publications
Data of HPV genotype including 16 high-risk HPV (HR-HPV) and 4 low-risk HPV from 38,397 women with normal cytology, 1341 women with cervical cytology abnormalities, and 223 women with ISCC were retrospectively evaluated by a hospital-based study. The prevalence of high-risk HPV (HR-HPV) was 6.51%, 41.83%, and 96.86% in women with normal cytology, cervical cytology abnormalities, and ISCC, respectively. The three most common HPV types were HPV-52 (1.76%), HPV-16 (1.28%), and HPV-58 (0.97%) in women with normal cytology, whereas the most prevalent HPV type was HPV-16 (16.85%), followed by HPV-52 (9.55%) and HPV-58 (7.83%) in women with cervical cytology abnormalities. Specifically, HPV-16 had the highest frequency in ASC-H (24.16%, 36/149) and HSIL (35.71%, 110/308), while HPV-52 was the most common type in ASC-US (8.28%, 53/640) and LSIL (16.80%, 41/244). HPV-16 (75.78%), HPV18 (10.31%), and HPV58 (9.87%) were the most common types in women with ISCC. These data might contribute to increasing the knowledge of HPV epidemiology and providing the guide for vaccine selection for women in Shantou.

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