Gene Summary

Gene:CISH; cytokine inducible SH2 containing protein
Aliases: CIS, G18, SOCS, CIS-1, BACTS2
Summary:The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:cytokine-inducible SH2-containing protein
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
Show (12)
Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

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

  • Spinal Cord Neoplasms
  • Stomach Cancer
  • Breast Cancer
  • United Kingdom
  • Gene Expression Profiling
  • ErbB Receptors
  • Estrogen Receptors
  • Tissue Fixation
  • Oligonucleotide Array Sequence Analysis
  • Gene Amplification
  • Uterine Cancer
  • Immunohistochemistry
  • Immunoenzyme Techniques
  • Gene Dosage
  • Skin Diseases
  • Cancer DNA
  • In Situ Hybridization
  • Adenocarcinoma
  • Tissue Array Analysis
  • Childhood Cancer
  • Lung Cancer
  • Risk Assessment
  • p53 Protein
  • Receptor, erbB-2
  • Sensitivity and Specificity
  • Young Adult
  • Staging
  • Biomarkers, Tumor
  • Reproducibility of Results
  • Chromogenic Compounds
  • Chromosome 17
  • Cancer Gene Expression Regulation
  • ERBB2
  • FISH
  • Mutation
  • Ductal Breast Carcinoma
  • Cancer RNA
  • Chromosome 3
  • Adolescents
  • Survival Rate
Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

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

Latest Publications: CISH (cancer-related)

Yang X, Li X, Quan X, et al.
Association Between Two Polymorphisms in the Promoter Region of miR-143/miR-145 and the Susceptibility of Lung Cancer in Northeast Chinese Nonsmoking Females.
DNA Cell Biol. 2019; 38(8):814-823 [PubMed] Related Publications
Lung cancer is known to cause high mortality and morbidity. The study aimed to explore the association between rs3733845 and rs3733846 polymorphisms in the promoter region of miR-143/145 and the risk of lung cancer among 575 nonsmoking cases and 575 cancer-free controls in a Chinese female population. We genotyped two single nucleotide polymorphisms (SNPs) in the promoter region of miR-143/145 in 575 cases and 575 controls using TaqMan allelic discrimination method. Logistic regression analysis was conducted to assess the association between polymorphisms in the promoter of miR-143/miR-145 and risk of lung cancer females. Crossover analysis was used to explore the interaction between the two SNPs and environmental risk factors (cooking oil fume exposure and passive smoking exposure). The results showed that both rs3733845 and rs3733846 polymorphisms were associated with an increased lung adenocarcinoma risk in dominant model (adjusted odds ratio [OR] = 1.329, 95% confidence intervals [CIs] = 1.026-1.723,

Chao XL, Wang LL, Liu R, et al.
Association between CA repeat polymorphism in IGF1 gene promoter and colorectal cancer risk in a native Chinese population.
Neoplasma. 2019; 2019 [PubMed] Related Publications
Insulin-like growth factor 1 (IGF1) is implicated in normal cell growth. It has been reported that IGF1 has a mitogenic and anti-apoptotic effect on colorectal cancer cells. However, results of studies on the association between cytosine-adenine (CA) repeat polymorphism in IGF1 gene promoter and colorectal cancer (CRC) risk are inconsistent. We aimed to evaluate the association between CA repeat polymorphism and CRC risk, as well as the relationship with the clinicopathological characteristics of CRC and circulating IGF1 level in a native Chinese population. There were 734 participants who were native Chinese in this case-control study, including 367 CRC cases and 367 age- and sex-matched controls. CA repeat polymorphism was genotyped by PCR and fragment analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated by unconditional logistic regression analysis. Circulating level of IGF1 in cases was significantly higher than that in controls (P = 0.002), particularly in males. Less than 38 CA repeats were associated with decreased CRC risk after adjusting for age and sex (37 versus 38 CA repeats: OR = 0.45; 95%CI = 0.26-0.78), especially in males. (CA)18/19 genotype showed approximately half reduced CRC risk comparing to (CA)19/19 genotype (OR = 0.46; 95%CI = 0.25-0.85). There was a significant association between the sum of CA repeats and degree of differentiation of CRC (P = 0.044). We observed a trend that circulating level of IGF1 in individuals with CA ≤ 38 repeats was lower than that in individuals with CA > 38 repeats with a borderline statistically significance in overall and males. In conclusion, our findings support the possible role of CA repeat polymorphism in CRC risk.

Zhang Y, Yang QX, Peng TT, et al.
Prognostic value of lncRNA FEZF1 antisense RNA 1 over-expression in oncologic outcomes of patients with solid tumors.
Medicine (Baltimore). 2019; 98(24):e15982 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1), as a novel lncRNA, was reported to be up-regulated in various cancers and involved in tumor progression. This study systematically assessed the prognostic value of FEZF1-AS1 in solid tumors.
METHODS: Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for eligible studies that evaluated the prognostic role of FEZF1-AS1 expression in cancer patients. Pooled hazard ratios (HRs) and combined odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. The meta-analysis was conducted using Stata/SE 14.1.
RESULTS: Fifteen original studies involving 1378 patients were enrolled. Pooled results showed that increased expression of FEZF1-AS1 significantly correlated with shorter overall survival (OS) in cancer patients (HR 2.04, 95% CI 1.60-2.47), and also shorter disease-free survival (DFS) (HR 2.08, 95% CI 1.27-2.89). Additionally, the combined ORs indicated that increased FEZF1-AS1 expression was significantly associated with lymph node metastasis (OR 3.35, 95% CI 1.98-5.67), distant metastasis (OR 3.10, 95% CI 1.86-5.15), poor tumor differentiation (OR 2.90, 95% CI 1.45-5.80), high depth of tumor invasion (OR 2.72, 95% CI 1.36-5.43), and advanced clinical stage (OR 2.76, 95% CI 1.75-4.35). Expression analysis using the Gene Expression Profiling Interactive Analysis database indicated that the expression of FEZF1-AS1 was higher in tumor tissues than that in the corresponding normal tissues. The results of survival analysis revealed that increased FEZF1-AS1 expression was correlated with poor OS and DFS in cancer patients.
CONCLUSIONS: LncRNA FEZF1-AS1 may serve as a valuable prognostic biomarker for clinical outcomes in various solid tumors.

Zhang X, Jin K, Luo JD, et al.
MicroRNA-107 inhibits proliferation of prostate cancer cells by targeting cyclin E1.
Neoplasma. 2019; 2019 [PubMed] Related Publications
Previous studies have reported that miR-107 could be utilized as a potential peripheral biomarker in prostate cancer (PCa). However, the specific functions of miR-107 in prostate cancer and its relevant mechanisms are still unknown. The aim of this research was to investigate the cellular functions of miR-107 in PCa and reveal the relevant mechanisms. MicroRNA tailing quantitative real-time PCR (qRT-PCR) was adopted to measure the expression of miR-107 in PCa cell line DU145 and PC3, as well as in normal prostate cell line RWPE-1. The miR-107 expression pattern in PCa tissues and paired peritumoral tissues were determined by Chromogenic In Situ Hybridization (CISH). Cell viability, colony formation, flow cytometry cell cycle and apoptosis, wound healing, and Transwell migration assays were performed to study the functions of miR-107 in PCa cells. Further, qRT-PCR, western blot analysis, and dual-luciferase reporter assays were conducted to verify the target of miR-107 in PCa. The results demonstrated that, miR-107 was down-regulated in PCa cells and tissues compared with normal prostate cells and peritumoral tissues, and over-expression of miR-107 suppressed the proliferation and induced G1/S arrest of PCa cells but had no effects on apoptosis or cell motility of PCa cells. MiR-107 was found to target cyclin E1 (CCNE1) in PCa cells by directly binding to its 3'-UTR. In conclusion, miR-107 could be a potential tumor suppressor in PCa, and the restoration of miR-107 might provide a new therapeutic option for PCa.

Xu X, Yang J, Zhou W, et al.
Genetic variations within alternative splicing associated genes are associated with breast cancer susceptibility in Chinese women.
Gene. 2019; 706:140-145 [PubMed] Related Publications
BACKGROUND: Alternative splicing regulates most of protein-coding genes by producing diverse messenger RNA transcripts; and mis-splicing events can induce aberrant protein isoforms that contribute to cancer development. It is possible that genetic variations in splicing associated genes may regulate the formation of transcripts and multiple protein isoforms by affecting the splice regulatory elements. In this study, we aimed to determine whether genetic variations in the crucial alternative-splicing genes were associated with breast cancer risk.
MATERIALS AND METHODS: A case-control study was conducted with 1064 breast cancer cases and 1073 healthy controls from China. A total of 16 tagging polymorphisms within three splicing factor-associated genes (SFRS3, ESRP1 and ESRP2) were genotyped by using Infinium BeadChip. The association between the polymorphisms and risk of breast cancer was evaluated by computing odds ratios (OR) and 95% confidence intervals (CIs).
RESULTS: The genotype distribution of rs2145048 in SFRS3 was different between cases and controls (Bonferroni corrected P = 0.022). After adjusting for age, age at menarche and menopausal status, the A allele of rs2145048 showed an inverse association with breast cancer risk in the additive model (adjusted OR = 0.81, 95% CI = 0.71-0.92, P = 0.001, Bonferroni corrected P = 0.016). In the stratification analysis, the association between rs2145048 A allele and breast cancer remained significant in subgroups of earlier menarche, older first born, premenopausal status, and ER/PR negative status.
CONCLUSIONS: This study provided the first evidence that SFRS3 rs2145048 was associated with breast cancer susceptibility in Chinese women, which might represent a biomarker to improve the identification of individuals at high risk of this malignancy.

Binabaj MM, Soleimani A, Rahmani F, et al.
Prognostic value of high mobility group protein A2 (HMGA2) over-expression in cancer progression.
Gene. 2019; 706:131-139 [PubMed] Related Publications
The high mobility group A2 (HMGA2; also called HMGI-C) gene is an architectural transcription factor that belonging to the high mobility group AT-hook (HMGA) gene family. HMGA2 is aberrantly regulated in several human tumors. Over-expression of HMGA2 is correlated with a higher risk of metastasis and an unfavorable prognosis in patients with cancer. We performed a meta-analysis to determine the clinic-pathological and prognostic value of HMGA2 overexpression in different human tumors. A comprehensive literature search was performed using PubMed, Embase, Cochrane Library, Scopus, MEDLINE, Google Scholar and ISI Web of Science. Hazard ratios (HRs)/odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of the association between HMGA2 expression and overall survival (OS)/progression free survival (PFS)/disease free survival (DFS). A total of 5319 patients with 19 different types of cancer from 35 articles were evaluated. Pooled data analysis indicated that increased HMGA2 expression in cancer patients predicted a poor OS (HR = 1.70; 95% CI = 1.6-1.81; P < 0.001; fixed-effect model). In subgroup analyses, high HMGA2 expression was particularly associated with poor OS in individuals with gastrointestinal (GI) cancer (HR = 1.89, 95% CI: 1.83-1.96; fixed-effect model) and HNSCC cancer (HR-1.78, 95%CI: 1.44-2.21; fixed-effect model). Over-expression of HMGA2 was associated with vascular invasion (OR = 0.16, 95% CI = 0.05-0.49; P = 0.001) and lymphatic invasion (OR = 1.89, 95% CI = 1.06-3.38; P = 0.032). Further studies should be conducted to validate the prognostic value of HMGA2 for patients with GI cancers.

Yun X, Bai Y, Li Z, et al.
rs895819 in microRNA-27a increase stomach neoplasms risk in China: A meta-analysis.
Gene. 2019; 707:103-108 [PubMed] Related Publications
BACKGROUND: Across the globe, gastric cancer is a significant public health problem. This meta-analysis was conducted to investigate the association of microRNA-27a (miRNA-27a) rs895819 with gastric cancer risk.
METHODS: The search of databases updated on October 10, 2018 included Pubmed, Embase, Cochrane Library and Web of science. Odds ratio (ORs) and 95% confidence interval (CIs) were calculated to assess the risk of tumor.
RESULTS: Overall meta-analysis suggested the miRNA-27a rs895819 was not related to the gastric carcinogenesis among all model including allele contrast (G vs A, pooled OR: 1.096, 95% CI: 0.962-1.249, P = 0.196), codominant model (GG vs AA, pooled OR: 1.124, 95% CI: 0.794-1.592, P = 0.590; AG vs AA, pooled OR: 1.101, 95% CI: 0.966-1.217, P = 0.060), dominant model (AG + GG vs AA, pooled OR: 1.123, 95% CI: 0.964-1.307, P = 0.136) and recessive model (GG vs AG + AA, pooled OR: 0.927, 95% CI: 0.673-1.278, P = 0.644). Interestingly, among different ethnicity group, significant relation between rs895819 and gastric cancer was observed in co-dominant model among Chinese population (AG vs AA, pooled OR: 1.158, 95% CI: 1.038-1.291, P = 0.008) but not some regions of European population (AG vs AA, pooled OR: 0.852, 95% CI: 0.632-1.148, P = 0.179).
CONCLUSIONS: Our results find that rs895819 contributed to occurrence of gastric cancer in co-dominant model in Chinese population.

Liu J, Zheng H, Ding Y, et al.
The level of Krüppel-like factor 8 expression predicts prognosis and metastasis in various carcinomas.
Medicine (Baltimore). 2019; 98(18):e15519 [PubMed] Free Access to Full Article Related Publications
BACKGROUND AND OBJECTIVE: Krüppel-like factor 8 (KLF8), a transcription factor, belongs to the KLF8 family. Currently, studies have shown that KLF8 is highly expressed in some tumors. However, the prognostic value and metastasis of KLF8 in cancers remain unclear. For the first time, we conducted meta-analysis to explore the relationship between KLF8 expression with prognosis and metastasis in various carcinomas patients.
METHODS: Web of Science, PubMed, Embase, and Cochrane Library were systematically searched for eligible articles. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to evaluate the prognostic value and metastasis of KLF8 expression in human cancer patients.
RESULTS: The result revealed that highly expression level of KLF8 was significantly associated with poor overall survival (OS) (HR = 1.56, 95% CI: 1.26-1.87). Meanwhile, this significant correlation was also observed in subgroup analysis stratified by cancer types, source of HR, sample size, follow-up (months). In addition, highly expression of KLF8 was also closely associated with metastasis (HR = 1.37, 95% CI: 0.57-2.17) and tumor node metastasis stage (HR = 1.58, 95% CI: 0.90-2.25) in carcinomas.
CONCLUSION: In summary, our meta-analysis indicates that overexpression of KLF8 may be associated with poor prognosis and higher incidence of metastasis in various carcinomas, and KLF8 may be used as a prognostic and metastatic indicator in human cancers.

Chen S, Chen L, Tan Y, Wang J
Association between rs20417 polymorphism in cyclooxygenase-2 and gastric cancer susceptibility: Evidence from15 case-control studies.
Medicine (Baltimore). 2019; 98(18):e15468 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Previous studies have reported an association between cyclooxygenase-2 (COX-2) polymorphism and gastric cancer (GC) susceptibility, but their results are controversial. This meta-analysis was intended to evaluate the relationship between the COX-2 rs20417 polymorphism and GC susceptibility in different ethnic groups.
METHODS: We searched PubMed, EMBASE, Web of Knowledge, and the Chinese Biomedical Database (CBM) for relevant case-control studies published up to October 6, 2018, which reported an association between the COX-2 rs20417 polymorphism and gastric cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association.
RESULTS: 15 papers detailing case-control studies were included in the analysis, which included a total of 2848 GC cases and 4962 healthy controls. The meta-analysis results indicated that the COX-2 rs20417 polymorphism was associated with increased GC susceptibility under allele (G vs C: OR = 1.67, 95%CI = 1.19-2.35, P = .003), heterozygous (GG vs CG: OR = 1.44, 95%CI = 1.03-2.02, P = .034), dominant (GC+CC vs GG: OR = 1.66, 95%CI = 1.18-2.34, P = .004), homozygous (GG vs CC:OR = 2.20, 95%CI = 1.07-4.54, P = .033), and recessive models (CC vs GG+CG:OR = 2.05, 95%CI = 1.09-3.85, P = .025). An analysis of ethnic subgroups revealed that the COX-2 rs20417 polymorphism was significantly associated with GC susceptibility in Asians under all 5 models (G vs C: OR = 2.22, 95%CI = 1.66-2.96, P < .001; GG vs CC: OR = 4.29, 95%CI = 1.94-9.50, P < .001; GG vs CG: OR = 1.86, 95%CI = 1.34-2.58, P < .001; CC vs GG+CG: OR = 3.73, 95%CI = 1.92-7.24, P < .001; GC+CC vs GG: OR = 2.20, 95%CI = 1.65-2.93, P < .001). Helicobacter pylori positive patients suffered a high risk of GC, compared to H pylori negative patients under the dominant model (OR = 3.09, 95%CI = 1.80-5.32, P < .001).
CONCLUSION: This meta-analysis of 15 case-control studies provides strong evidence that the COX-2 rs20417 polymorphism increases the risk of GC susceptibility in general populations, especially in Asians. Helicobacter pylori positive patients and those with the COX-2 rs20417 polymorphism had a higher risk of developing GC.

Zhang Y, Chen J, Xue Q, et al.
Prognostic Significance of MicroRNAs in Glioma: A Systematic Review and Meta-Analysis.
Biomed Res Int. 2019; 2019:4015969 [PubMed] Free Access to Full Article Related Publications
Purpose: Different microRNAs (miRs) have been demonstrated to relate with the outcome of glioma patients, while the conclusions are inconsistent. We perform a meta-analysis to clarify the relationship between different miRs and prognosis of glioma.
Methods: Related studies were retrieved from PubMed, Embase, and Cochrane Library. Pooled hazard ratios (HRs) of different miRs expression for survival and 95% confidence intervals (CIs) were calculated using random-effects model.
Results: A total of 15 miRs with 4708 glioma patients were ultimately included. Increased expression of miR-15b (HR, 1.584; 95% CI, 1.199-2.092), 21 (HR, 1.591; 95% CI, 1.278-1.981), 148a (HR, 1.122; 95% CI, 1.023-1.231), 196 (HR, 1.877; 95% CI, 1.033-3.411), 210 (HR, 1.251; 95% CI, 1.010-1.550), and 221 (HR, 1.269; 95% CI, 1.054-1.527) or decreased expression of miR-106a (HR, 0.809; 95% CI, 0.655-0.998) and 124 (HR, 0.833; 95% CI, 0.729-0.952) was correlated with poor outcome of glioma patients.
Conclusions: miR-15b, 21, 148a, 196, 210, 221, 106a, and 124 are valuable biomarkers for the prognosis of glioma which might be used in clinical settings.

Świerczewska M, Sterzyńska K, Wojtowicz K, et al.
PTPRK Expression Is Downregulated in Drug Resistant Ovarian Cancer Cell Lines, and Especially in ALDH1A1 Positive CSCs-Like Populations.
Int J Mol Sci. 2019; 20(8) [PubMed] Free Access to Full Article Related Publications

Yu J, Yan Y, Hua C, Ming L
Upregulation of lncRNA SNHG1 is associated with metastasis and poor prognosis in cancers: A meta-analysis.
Medicine (Baltimore). 2019; 98(16):e15196 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Accumulating evidence suggested that the expression level of long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) was upregulated in various cancers, and high expression of SNHG1 was associated with metastasis and prognosis in patients with cancer.The relationship between SNHG1 expression and metastasis or prognosis in malignant tumors was investigated in this meta-analysis.
METHODS: A systematic search was performed in PubMed, Web of Science, and Cochrane Library from inception until May 31, 2018. Hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CIs) were calculated to demonstrate prognostic value of SNHG1 using Stata 12.0 software.
RESULTS: A total of 10 studies including 1129 patients were finally enrolled in the meta-analysis based on the inclusion and exclusion criteria. Increased SNHG1 expression was significantly associated with lymph node metastasis (OR = 3.28, 95% CI = 2.02-5.33) and advanced TNM stage (OR = 0.26, 95% CI = 0.16-0.43). Moreover, high expression of SNHG1 could predict poor overall survival (HR = 2.32, 95% CI = 1.90-2.83), event-free survival (HR = 1.58, 95% CI = 1.06-2.35), recurrence-free survival (HR = 2.15, 95% CI = 1.23-3.77), progression-free survival (HR = 2.75, 95% CI = 1.70-4.46), and disease-free survival (HR = 1.93, 95% CI = 1.10-3.40) in patients with cancer.
CONCLUSION: The present meta-analysis demonstrated that upregulation of lncRNA SNHG1 might serve as a useful prognostic biomarker in various cancers.

Deng S, Ren ZJ, Jin T, et al.
Contribution of prostate stem cell antigen variation rs2294008 to the risk of bladder cancer.
Medicine (Baltimore). 2019; 98(16):e15179 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Number of studies have been performed to evaluate the relationship between prostate stem cell antigen (PSCA) variation rs2294008 and bladder cancer risk, but the sample size was small and the results were conflicting. This meta-analysis was conducted to comprehensively evaluate the overall association.
METHODS: Pubmed, Web of science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang and Weipu databases were searched before June 30, 2018. The strength of associations was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). All of the statistical analyses were conducted using Review Manager 5.3 and Stata 14.0.
RESULTS: Ten studies involved 14,021 cases and 26,871 controls. Overall, significant association was observed between the PSCA gene variant rs2294008 polymorphism and bladder cancer (T vs C: OR = 1.16, 95%CI = 1.12-1.20; TT vs CC: OR = 1.32, 95%CI = 1.24-1.41; TT vs CT+CC: OR = 1.15, 95%CI = 1.09-1.22; TT+CT vs CC: OR = 1.27, 95%CI = 1.21-1.34). In subgroup analysis by ethnic group, a statistically significant association was observed in Asians (T vs C: OR = 1.23, 95%CI = 1.15-1.31) and Caucasians (T vs C: OR = 1.14, 95%CI = 1.10-1.18). The sensitivity analysis confirmed the reliability and stability of the meta-analysis.
CONCLUSION: Our meta-analysis supports that the PSCA gene variant rs2294008 polymorphism might contribute to individual susceptibility to bladder cancer.

Zhu L, Ma G, Liu J, et al.
Prognostic significance of nuclear Yes-associated protein 1 in patients with nonsmall cell lung cancer: A systematic review and meta-analysis.
Medicine (Baltimore). 2019; 98(16):e15069 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Nuclear Yes-associated protein 1 (YAP1) has often been regarded as an adverse prognostic indicator in various tumors. Recent studies have associated YAP1 with unfavorable prognosis in nonsmall cell lung cancer (NSCLC). However, due to small sample sizes, the prognostic value of nuclear YAP1 in NSCLC patients is not well understood. In the present study, we evaluated the prognostic role of nuclear YAP1 in NSCLC patients via a systematic review and meta-analysis.
METHODS: We searched the PubMed, EMBASE, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Databases for papers investigating the prognostic significance of nuclear YAP1 expression in NSCLC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated with reference to overall survival (OS) and progression-free survival (PFS) of NSCLC patients to provide synthesized estimates of the effects of nuclear YAP1 expression.
RESULTS: Among 414 cases, higher nuclear YAP1 expression presented as a predictive factor of poorer OS (HR = 1.52; 95% CI: 1.11-2.08; P = .01; I = 0.0%) and decreased PFS (HR = 2.11; 95% CI: 1.52-2.93; P < .001; I = 44.2%) in NSCLC patients. Subgroup analysis revealed shortened OS (HR = 1.63; 95% CI: 1.14-2.34; P = .007; I = 0.0%) and worse PFS (HR = 2.25; 95% CI: 1.53-3.30; P < .001; I = 0.0%) in patients from Asia with higher nuclear YAP1 expression. Prognosis was also worse in patients with III-IV stage cancer (PFSHR = 2.09; 95% CI: 1.45-3.01; P < .001; I = 58.1%) and in patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) (OS HR = 1.59; 95% CI: 1.00-2.51; P = .048; I = 15.5%, and PFS HR = 2.35, 95% CI: 1.62-3.42; P < .001; I = 0.0%).
CONCLUSION: High expression of nuclear YAP1 was associated with shorter survival outcome in patients with NSCLC.

Xu S, Wang P, Zhang J, et al.
Ai-lncRNA EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions in human cancer.
Mol Cancer. 2019; 18(1):89 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The biology function of antisense intronic long noncoding RNA (Ai-lncRNA) is still unknown. Meanwhile, cancer patients with paclitaxel resistance have limited therapeutic options in the clinic. However, the potential involvement of Ai-lncRNA in paclitaxel sensitivity remains unclear in human cancer.
METHODS: Whole transcriptome sequencing of 33 breast specimens was performed to identify Ai-lncRNA EGOT. Next, the role of EGOT in regulation of paclitaxel sensitivity was investigated. Moreover, the mechanism of EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions was investigated in detail. Furthermore, upstream transcriptional regulation of EGOT expression was also investigated by co-immunoprecipitation and chromatin immunoprecipitation. Finally, clinical breast specimens in our cohort, TCGA and ICGC were applied to validate the role of EGOT in enhancing of paclitaxel sensitivity.
RESULTS: EGOT enhances autophagosome accumulation via the up-regulation of ITPR1 expression, thereby sensitizing cells to paclitaxel toxicity. Mechanistically, on one hand, EGOT upregulates ITPR1 levels via formation of a pre-ITPR1/EGOT dsRNA that induces pre-ITPR1 accumulation to increase ITPR1 protein expression in cis. On the other hand, EGOT recruits hnRNPH1 to enhance the alternative splicing of pre-ITPR1 in trans via two binding motifs in EGOT segment 2 (324-645 nucleotides) in exon 1. Moreover, EGOT is transcriptionally regulated by stress conditions. Finally, EGOT expression enhances paclitaxel sensitivity via assessment of cancer specimens.
CONCLUSIONS: These findings broaden comprehensive understanding of the biology function of Ai-lncRNAs. Proper regulation of EGOT may be a novel synergistic strategy for enhancing paclitaxel sensitivity in cancer therapy.

Nitta H, Kelly B
Chromogenic Tissue-Based Methods for Detection of Gene Amplifications (or Rearrangements) Combined with Protein Overexpression in Clinical Samples.
Methods Mol Biol. 2019; 1953:301-314 [PubMed] Related Publications
Immunohistochemistry (IHC) is a well-established, tissue-based assay for the visualization of target proteins. For analysis of DNA targets, chromogenic in situ hybridization (CISH) applications have significant advantages over traditional fluorescence in situ hybridization (FISH). CISH slides can be analyzed using a regular light microscope, while FISH slides require the use of a specialized fluorescence microscope in a dark room. CISH slides allow observers to correlate the gene status (gene amplifications, gene rearrangements, and gene deletions) in the context of tissue morphology better than FISH slides. Recently, a combination of IHC and CISH assays (gene-protein assay, GPA) was developed to study the relationship between gene status and protein expression on the same tissue section. CISH and GPA applications can be optimized using an automated tissue slide processing system to generate reproducible results for a long and complex assay protocol. GPA applications are an ideal approach for tumor status and heterogeneity analyses for research and clinical investigations.

Minlikeeva AN, Cannioto R, Jensen A, et al.
Joint exposure to smoking, excessive weight, and physical inactivity and survival of ovarian cancer patients, evidence from the Ovarian Cancer Association Consortium.
Cancer Causes Control. 2019; 30(5):537-547 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated.
METHODS: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (n = 7,022). Using age- and stage-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors.
RESULTS: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR = 1.37; 95% CI 1.10-1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR = 1.28; 95% CI 1.08-1.52, and HR = 1.26; 95% CI 1.04-1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS.
CONCLUSIONS: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients' survival.

Xi Y, Zhang X, Yang Z, et al.
Prognositic significance of P-cadherin expression in breast cancer: Protocol for a meta-analysis.
Medicine (Baltimore). 2019; 98(12):e14924 [PubMed] Related Publications
BACKGROUND: P-cadherin is a calcium-dependent cell-cell adhesion glycoprotein. It has been implicated in invasiveness and metastasis. However, the clinical prognostic value of overexpression of P-cadherin in patients with breast cancer (BC) remains unsettled.
METHODS: A systematic literature search will be performed in all available databases to quantitatively review eligible studies and identify all relevant data, which could be used to detect the relationship between overexpression of P-cadherin and overall survival (OS), disease-free survival (DFS), and clinicopathological parameters. Hazard ratio and 95% confidence intervals (CIs) or P value will be employed as effect measures to estimate the correlation between P-cadherin and the oncologic outcomes including overall survival (OS), disease-free survival (DFS). Odds ratios (ORs) and the 95% CIs will be evaluated for the pooled analysis of the correlation between P-cadherin expression and clinicopathological features. We will use the Review Manager (Revman) 5.3.5 software (Cochrane Community, London, United Kingdom) and STATA 14 software (version 14.0; Stata Corp, College Station, TX) to perform the meta-analysis to calculate the data.
RESULTS: The review will provide a high-quality synthesis of current evidence of the prognostic role of P-cadherin in BCs. The results will be published in a peer-reviewed journal.
CONCLUSION: We hope that the results of this study will provide significant evidence to assess whether the expression of P-cadherin is associated with poor prognosis in patients with BC.
PROSPERO REGISTRATION NUMBER: This meta-analysis protocol has been registered in the PROSPERO network with registration number: CRD42019119880.

Wu J, Zhang W, Cai J, et al.
Influence of IL-1R2 polymorphisms on endometrial cancer susceptibility in the Chinese Han population.
Mol Genet Genomic Med. 2019; 7(5):e650 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Recently, many studies have identified that genetic factor plays a crucial role in endometrial cancer development. The purpose of this study is to investigate the influence of single nucleotide polymorphisms (SNPs) of IL-1R2 on endometrial cancer susceptibility.
METHODS: We performed a case-control study that included 293 patients with endometrial cancer and 579 healthy controls. Six SNPs in the IL-1R2 gene were genotyped using the Agena MassARRAY platform. Genetic models and haplotype analyses were used to assess the association between SNPs and endometrial cancer risk by computing odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS: Overall analysis results found that two SNPs (rs4851527 and rs3218896) and haplotypes TGTC and TACT were significantly associated with endometrial cancer risk. Stratified analysis by age showed that rs2072472 was associated with endometrial cancer risk in age >54 subgroup.
CONCLUSIONS: These findings suggested that IL-1R2 polymorphisms may contribute to the development of endometrial cancer. Further studies are required to confirm the results.

Wei L, Niu F, Wu J, et al.
Association study between genetic polymorphisms in folate metabolism and gastric cancer susceptibility in Chinese Han population: A case-control study.
Mol Genet Genomic Med. 2019; 7(5):e633 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Gastric cancer (GC), the second leading cause of cancer mortality behind lung cancer worldwide, is caused by both genetic and environmental factors. In this study, we evaluated the association between the genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTR), and methyltransferase reductase (MTRR) genes and ischemic stroke risk in Chinese population.
METHODS: A case-control study was conducted including 681 patients with GC and 756 healthy controls. Chi-squared test/Fisher's exact test and genetic model were used to evaluate associations. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression.
RESULTS: In the allele model, using the chi-square test, we found that the rs1532268 in MTRR with a minor allele T was significantly associated with increased risk of GC (OR = 1.24, 95% CI, 1.00-1.53; p = 0.048). In the genetic model analysis, we identified that the single-nucleotide polymorphism of the rs1801133 in MTHFR could increase the GC risk in the recessive model (OR = 1.31, 95% CI, 1.01-1.70; p = 0.042) and log-additive model (OR = 1.19, 95% CI, 1.02-1.38; p = 0.025). In MTHFR, a strong linkage of rs2274976 and rs1801133 was detected. The haplotype "GC" in the MTHFR gene was found to prominently increase the risk of GC (OR = 1.26, 95% CI: 1.07-1.47; p = 0.005). Other haplotypes did not display the correlativity.
CONCLUSION: This study suggested that MTR and MTHFR polymorphisms may contribute to increase the risk of GC.

Pin-On P, Aporntewan C, Siriluksana J, et al.
Targeting high transcriptional control activity of long mononucleotide A-T repeats in cancer by Argonaute 1.
Gene. 2019; 699:54-61 [PubMed] Related Publications
Epigenetic regulatory changes alter the gene regulation function of DNA repeat elements in cancer and consequently promote malignant phenotypes. Some short tandem repeat sequences, distributed throughout the human genome, can play a role as cis-regulatory elements of the genes. Distributions of tandem long (≥10) and short (<10) A-T repeats in the genome are different depending on gene functions. Long repeats are more commonly found in housekeeping genes and may regulate genes in harmonious fashion. Mononucleotide A-repeats around transcription start sites interact with Argonaute proteins (AGOs) to regulate gene expression. miRNA-bound AGO alterations in cancer have been reported; consequently, these changes would affect genes containing mononucleotide A- and T-repeats. Here, we showed an unprecedented hallmark of gene regulation in cancer. We evaluated the gene expression profiles reported in the Gene Expression Omnibus and found a high density of 13-27 A-T repeats in the up-regulated genes in malignancies derived from the bladder, cervix, head and neck, ovary, vulva, breast, colon, liver, lung, prostate, kidney, thyroid, adrenal gland, bone, blood cells, muscle and brain. Transfection of cell-penetrating protein tag AGO1 containing poly uracils (CPP-AGO1-polyUs) to the lung cancer cell lines altered gene regulation depending on the presence of long A-T repeats. CPP-AGO1-polyUs limited cell proliferation and the ability of a cancer cell to grow into a colony in lung cancer cell lines. In conclusion, long A-T repeats up-regulated many genes in cancer that can be targeted by AGO1 to change the expression of many genes and limited cancer growth.

Song Y, Yang Y, Liu L, Liu X
Association between five polymorphisms in vascular endothelial growth factor gene and urinary bladder cancer risk: A systematic review and meta-analysis involving 6671 subjects.
Gene. 2019; 698:186-197 [PubMed] Related Publications
BACKGROUND: Vascular endothelial growth factor (VEGF) gene plays a key role in angiogenesis and tumor growth. The relationship between VEGF gene polymorphisms and bladder cancer (BCa) risk was studied extensively in recent years. However, the currently available results are controversial. To ascertain whether VEGF polymorphisms are associated with the susceptibility to BCa, we conducted this systematic review and meta-analysis.
MATERIALS AND METHODS: Relevant studies were collected systemically from PubMed, Medline, Embase, Web of Science databases and the Cochrane Library. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated using random or fixed effects models by Stata statistical software. This systematic review protocol was registered at International prospective register of systematic reviews (PROSPERO) under number CRD42018099279.
RESULTS: A total of eight articles including twenty case-control studies with 3206 BCa cases and 3645 controls were enrolled for this meta-analysis. By pooling all eligible studies, we found that rs3025039, rs833052 and rs25648 polymorphisms were significantly associated with BCa risk. However, in subgroup analyses by stage, we identified a decreased association between the rs699947 A-allele and Muscle-invasive Bladder Cancer (MIBC) under allele contrast, homozygous and recessive genetic models (A vs C: OR = 0.76; AA vs CC: OR = 0.49, 95%CI = 0.27-0.90, I
CONCLUSION: Our meta-analysis suggested that rs3025039 (C > T), rs833052 (C > A) and rs25648 (C > T) polymorphisms of VEGF gene increased susceptibility to BCa risk. And our study also demonstrated homozygous TT genotype in rs3025039, homozygous AA genotype in rs833052 and homozygous TT genotype in rs25648 were significantly relevant to elevated BCa risk. In the meanwhile, it is worth noting that rs699947 (C > A) A-allele should be thought as a protective factor for MIBC.

Cai J, Cui K, Niu F, et al.
Genetics of IL6 polymorphisms: Case-control study of the risk of endometrial cancer.
Mol Genet Genomic Med. 2019; 7(4):e00600 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Endometrial cancer is the most common gynaecological malignancy. Cytokines gene may be important in endometrial cancer development. This study sought to investigate whether the IL4, IL6 two gene genetic variants were associated with susceptibility to endometrial cancer (EC) in Hainan Chinese Han women by a hospital-based study.
METHODS: The genetic polymorphisms for IL4 and IL6 were analyzed by Agena MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression.
RESULTS: We observed a significant increase in risk of endometrial cancer of rs1524107 (IL6) (T/C, OR = 1.61, 95% CI = 1.09-2.37, p = 1.55 × 10
CONCLUSION: This study demonstrated that IL6 gene polymorphisms are significantly associated with increased EC susceptibility in Hainan Chinese Han women.

Wang F, Diao XY, Zhang X, et al.
Identification of genetic alterations associated with primary resistance to EGFR-TKIs in advanced non-small-cell lung cancer patients with EGFR sensitive mutations.
Cancer Commun (Lond). 2019; 39(1):7 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Identification of activated epidermal growth factor receptor (EGFR) mutations and application of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have greatly changed the therapeutic strategies of non-small-cell lung cancer (NSCLC). However, the long-term efficacy of EGFR-TKI therapy is limited due to the development of drug resistance. The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR-TKIs in advanced NSCLC patients with activated EGFR mutations.
METHODS: We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR-TKI treatment, from April 2004 and March 2011, at the Sun Yat-sen University Cancer Center. Several genetic alterations associated with the efficacy of EGFR-TKIs, including the alterations in BIM, ALK, KRAS, PIK3CA, PTEN, MET, IGF1R, and ROS1, were detected by the routine clinical technologies. The progression-free survival (PFS) and overall survival (OS) were compared between different groups using Kaplan-Meier survival analysis with the log-rank test. A Cox regression model was used to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (95% CIs) associated with the PFS and OS.
RESULTS: Among the investigated patients, 169 NSCLC patients harbored EGFR-sensitive mutations. EGFR-mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN (P = 0.003 for PFS, and P = 0.034 for OS). In the combined molecular analysis of EGFR signaling pathway and resistance genes, we found that EGFR-mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations (P < 0.001). A Cox proportional regression model determined that PTEN deletion (HR = 4.29,95% CI = 1.72-10.70) and low PTEN expression (HR = 1.96, 95% CI = 1.22-3.13), MET FISH + (HR = 2.83,95% CI = 1.37-5.86) were independent predictors for PFS in patients with EGFR-TKI treatment after adjustment for multiple factor.
CONCLUSIONS: We determined that the coexistence of genetic alterations in cancer genes may explain primary resistance to EGFR-TKIs.

Bien SA, Su YR, Conti DV, et al.
Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.
Hum Genet. 2019; 138(4):307-326 [PubMed] Free Access to Full Article Related Publications
Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10

Gao S, Lin Z, Li C, et al.
lncINS-IGF2 Promotes Cell Proliferation and Migration by Promoting G1/S Transition in Lung Cancer.
Technol Cancer Res Treat. 2019; 18:1533033818823029 [PubMed] Free Access to Full Article Related Publications
Long noncoding RNAs are capable of regulating gene expression at multiple levels. These RNA molecules are also involved in a variety of physiological and pathological processes. Emerging data demonstrate that a series of differentially expressed long noncoding RNAs are implicated in tumorigenesis. In the present study, we used microarray analysis to identify long noncoding RNAs that are dysregulated in non-small-cell lung cancer when compared to normal lung tissues. Accordingly, we performed quantitative real-time polymerase chain reaction to analyze the levels of long noncoding RNA and the cis target gene. We further found the oncogene property of long noncoding RNA that long noncoding RNA downexpression inhibits non-small-cell lung cancer cells proliferation and migration based on 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and colony formation assays and wound healing as well as transwell assays. The influence of long noncoding RNA on cell cycle of non-small-cell lung cancer cells is also analyzed by flow cytometry. Among the dysregulated long noncoding RNAs, we identified INS-IGF2 readthrough, transcript variant 1, noncoding RNA (NR_003512.3) is upregulated in non-small-cell lung cancer tissues, the cis gene of which is insulin-like growth factor 2 gene hinted by bioinformatics analysis. We also observed that downregulation of INS-IGF2 readthrough, transcript variant 1, noncoding RNA reduces insulin-like growth factor 2 messenger RNA expression. Furthermore, INS-IGF2 readthrough, transcript variant 1, noncoding RNA downregulation suppresses non-small-cell lung cancer cell proliferation and migration. This downregulation results in a concomitant inhibition of the G1/S transition in non-small-cell lung cancer cells. Our findings suggest that INS-IGF2 readthrough, transcript variant 1, noncoding RNA may be an oncogene involved in the development of lung cancer. Therefore, we speculate that INS-IGF2 readthrough, transcript variant 1, noncoding RNA represents a potential therapeutic target for lung cancer.

Hu X, Chen J
Association of angiotensin ІІ type 1 receptor gene A1166C polymorphism with cancer risk: An updated meta-analysis.
J Renin Angiotensin Aldosterone Syst. 2019 Jan-Mar; 20(1):1470320319827207 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE:: The association between angiotensin II type 1 receptor ( AGTR1) gene A1166C polymorphism and cancer risk has been investigated in many studies. However, the results have been inconclusive. A meta-analysis was performed to obtain a more precise estimation of the relationship.
METHODS:: The PubMed and China National Knowledge Infrastructure databases were searched for published literature. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strengths of association.
RESULTS:: Ten studies, including 1553 patients and 1904 controls, were included in the meta-analysis. Overall, there were no significant associations between the AGTR1 gene A1166C polymorphism and cancer risk in the general population (CC vs AA: OR = 1.09, 95% CI = 0.50-2.37; AC vs AA: OR = 1.54, 95% CI = 0.81-2.91; dominant model: OR = 1.46, 95% CI = 0.77-2.79; recessive model: OR = 1.12, 95% CI = 0.84-1.49). In a subgroup analysis by nationality and cancer type, the results also showed no association between this polymorphism and cancer risk.
CONCLUSIONS:: This meta-analysis demonstrated that the AGTR1 gene A1166C polymorphism does not appear to be related to the risk of cancer.

Pyfrom SC, Luo H, Payton JE
PLAIDOH: a novel method for functional prediction of long non-coding RNAs identifies cancer-specific LncRNA activities.
BMC Genomics. 2019; 20(1):137 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments.
RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods. PLAIDOH integrates transcriptome, subcellular localization, enhancer landscape, genome architecture, chromatin interaction, and RNA-binding (eCLIP) data and generates statistically defined output scores. PLAIDOH's approach identifies and ranks functional connections between individual lncRNA, coding gene, and protein pairs using enhancer, transcript cis-regulatory, and RNA-binding protein interactome scores that predict the relative likelihood of these different lncRNA functions. When applied to 'omics datasets that we collected from lymphoma patients, or to publicly available cancer (TCGA) or ENCODE datasets, PLAIDOH identified and prioritized well-known lncRNA-target gene regulatory pairs (e.g., HOTAIR and HOX genes, PVT1 and MYC), validated hits in multiple lncRNA-targeted CRISPR screens, and lncRNA-protein binding partners (e.g., NEAT1 and NONO). Importantly, PLAIDOH also identified novel putative functional interactions, including one lymphoma-associated lncRNA based on analysis of data from our human lymphoma study. We validated PLAIDOH's predictions for this lncRNA using knock-down and knock-out experiments in lymphoma cell models.
CONCLUSIONS: Our study demonstrates that we have developed a new method for the prediction and ranking of functional connections between individual lncRNA, coding gene, and protein pairs, which were validated by genetic experiments and comparison to published CRISPR screens. PLAIDOH expedites validation and follow-on mechanistic studies of lncRNAs in any biological system. It is available at .

Shi XY, Huang AP, Xie DW, Yu XL
Association of vitamin D receptor gene variants with polycystic ovary syndrome: a meta-analysis.
BMC Med Genet. 2019; 20(1):32 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women. Multiple susceptible gene as well as environmental factors and their interaction each other are contributed to the PCOS risk. Several case-control studies have researched the associations of the vitamin D receptor gene (VDR) polymorphisms with PCOS susceptibility, but the jury is still out. Here, we carried out a meta-analysis to clarify polymorphisms between ApaI (C/A) (rs7975232), BsmI (G/A) (rs1544410), FokI (C/T) (rs10735810), TaqI (T/C) (rs731236) and Tru9I (G/A) (rs757343) in the VDR gene and PCOS susceptibility based on relative lager sample size.
METHODS: English database of PubMed and Embase, and Chinese database of Wanfang and China National Knowledge Infrastructure (CNKI) databases were retrivaled for the relationship between VDR gene variates and PCOS susceptibility published before 31th, May 2018. Crude odds ratios (ORs) and its 95% confidence intervals (95% CIs) in different comparisons were used to detected the strength of the association. All the statistical analyses of the present meta-analysis were performed by STATA version 12.0 software.
RESULTS: Totally, 3587 (PCOS group 1922; control group 1665) participants from 13 studies were included which met our inclusion criteria. A statistically significant association between VDR ApaI (rs7975232) polymorphism and PCOS susceptibility (C vs. A: OR = 1.19, 95%CI = 1.06~1.34, P = 0.004) was found in the overall population. After stratified by ethnicity, we showed that there is a significant association between VDR ApaI (rs7975232) polymorphism and susceptibility to PCOS in the Asian (C vs. A: OR = 1.21, 95%CI = 1.04~1.42, P = 0.016) population, but this association was not found in the Caucasian population. Additionally, a significant relationship between VDR BsmI (rs1544410) variates with PCOS susceptibility in the Asian (G vs. A: OR = 1.27, 95%CI = 1.06~1.53, P = 0.011) population, but this association was not found in the Caucasian population. We didn't find any association between VDR FokI (rs2228570), VDR TaqI (rs731236), VDR Tru9I (rs757343) and PCOS susceptibility in the overall and the subgroup populations.
CONCLUSIONS: Our findings demonstrated that VDR ApaI (rs7975232) and VDR BsmI (rs1544410) polymorphisms are correlated with susceptibility to PCOS in the Asian population and VDR TaqI (rs731236), VDR FokI (rs2228570), VDR Tru9I (rs757343) did not reveal a relationship with the PCOS susceptibility.

Moazeni-Roodi A, Ghavami S, Hashemi M
Survivin rs9904341 polymorphism significantly increased the risk of cancer: evidence from an updated meta-analysis of case-control studies.
Int J Clin Oncol. 2019; 24(4):335-349 [PubMed] Related Publications
AIMS: Survivin, a member of inhibitor of apoptosis protein family, is involved in the regulation of cell cycle and apoptosis. Several studies inspected the association between survivin polymorphisms and the risk of various cancers, but the findings remain controversial. We conducted a meta-analysis intending to certify the association between survivin polymorphisms and cancer risk.
METHODS: All analyses were achieved using RevMan 5.3 software and STATA 14.1 software. Eligible studies were collected by comprehensive literature searching Web of Science, PubMed, Scopus, and Google scholar databases. Pooled estimates of odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the overall impact of survivin polymorphisms on cancer risk.
RESULTS: The overall analysis indicates that survivin rs9904341 polymorphism significantly increased the risk of cancer in homozygous codominant (OR 1.41, 95% CI 1.19-1.68, p = 0.0001, CC vs GG), dominant (OR 1.22, 95% CI 1.07-1.40, p = 0.003, CG+CC vs GG), recessive (OR 1.34, 95% CI 1.18-1.52, p < 0.0001, CC vs CG+GG), and allele (OR 1.20, 95% CI 1.09-1.31, p = 0.0001, C vs G) inheritance models tested. Stratified based on ethnicity revealed that rs9904341 variant significantly increased the risk of cancer in the Asian population. The findings did not support an association between rs1042489, rs2071214, rs8073069, and rs17878467 polymorphisms and risk of cancer.
CONCLUSIONS: The current study suggests that the survivin rs9904341 polymorphism may be associated with the risk of cancer either overall or in the Asian population. However, further larger and well-designed studies are warranted to evaluate this association in detail.

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