Abstract 1121: Analysis of gene expression changes as a function of PBRM1, BAP1, and SETD2 mutation status clear cell renal cell carcinoma in TCGA tumors

Abstract Background The four most commonly-mutated genes in clear cell renal cell carcinoma (ccRCC) tumors are BAP1, PBRM1, SETD2 and VHL. And, there are currently 14 known RCC germline variants that have been reproducibly shown to be associated with RCC risk. However, the association of germline genetics with tumor genetics and clinical aggressiveness are unknown. Methods We analyzed 420 ccRCC patients from The Cancer Genome Atlas. Molecular subtype was determined based on acquired mutations in BAP1, PBRM1, SETD2 and VHL. Aggressive subtype was defined clinically using Mayo SSIGN score and molecularly using the ccA/ccB gene expression subtype. Publically-available Hi-C data were used to link germline risk variants with candidate target genes. Results The 8q24 variant rs35252396 was significantly associated with VHL mutation status (OR = 1.6, p = 0.0037) and SSIGN score (OR = 1.9, p = 0.00094), after adjusting for multiple comparisons. We observed that, while some germline variants have interactions with nearby genes, some variants demonstrate long-range interactions with target genes. Conclusions These data further demonstrate the link between rs35252396, HIF pathway and ccRCC clinical aggressiveness, providing a more comprehensive picture of how germline genetics and tumor genetics interact with respect to tumor development and progression.

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Personalised drug repositioning for Clear Cell Renal Cell Carcinoma using gene expression

Scientific Reports ◽

10.1038/s41598-018-23195-8 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 8

Author(s):

Karel K. M. Koudijs ◽

Anton G. T. Terwisscha van Scheltinga ◽

Stefan Böhringer ◽

Kirsten J. M. Schimmel ◽

Henk-Jan Guchelaar

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Drug Repositioning ◽

Cell Renal Cell Carcinoma

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Abstract A110: Kinase gene expression profiles are associated with clinical outcomes in clear cell renal cell carcinoma patients

10.1158/1940-6207.prev-08-a110 ◽

2008 ◽

Author(s):

Michelle Hildebrandt ◽

Pheroze Tamboli ◽

Maosheng Huang ◽

Yuanqing Ye ◽

Ju-Seog Lee ◽

...

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Clinical Outcomes ◽

Renal Cell ◽

Clear Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Cell Renal Cell Carcinoma ◽

Kinase Gene

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Prognostic Value of DNA Methylation-Driven Genes in Clear Cell Renal Cell Carcinoma: A Study Based on Methylation and Transcriptome Analyses

Disease Markers ◽

10.1155/2020/8817652 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Maolin Hu ◽

Jiangling Xie ◽

Huiming Hou ◽

Ming Liu ◽

Jianye Wang

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Risk Score ◽

Renal Cell ◽

Methylation Level ◽

Cox Regression ◽

Clear Cell ◽

Cell Renal Cell Carcinoma

Background. Few previous studies have comprehensively explored the level of DNA methylation and gene expression in ccRCC. The purpose of this study was to identify the key clear cell renal cell carcinoma- (ccRCC-) related DNA methylation-driven genes (MDG) and to build a prognostic model based on the level of DNA methylation. Methods. RNA-seq transcriptome data and DNA methylation data were obtained from The Cancer Genome Atlas. Based on the MethylMix algorithm, we obtain ccRCC-related MDG. The univariate and multivariate Cox regression analyses were employed to investigate the correlation between patient overall survival and the methylation level of each MDG. Finally, a prognosis risk score was established based on a linear combination of the regression coefficient derived from the multivariate Cox regression model (β) multiplied with the methylation level of the gene. Results. 19 ccRCC-related MDG were identified. Three MDG (NCKAP1L, EVI2A, and BATF) were further screened and integrated into a prognostic risk score model, risk score=3.710∗methylation level of NCKAP1L+−3.892∗methylation level of EVI2A+−3.907∗methylation level of BATF. The risk model was independent from conventional clinical characteristics as a prognostic factor for ccRCC (HR=1.221, 95% confidence interval: 1.063–1.402, and P=0.005). The joint survival analysis showed that the gene expression and methylation levels of the prognostic genes EVI2A and BATF were significantly related with prognosis. Conclusion. This study provided an important bioinformatics foundation for in-depth studies of ccRCC DNA methylation.

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LRRC19—A Bridge between Selenium Adjuvant Therapy and Renal Clear Cell Carcinoma: A Study Based on Datamining

Genes ◽

10.3390/genes11040440 ◽

2020 ◽

Vol 11 (4) ◽

pp. 440

Author(s):

Yitong Zhang ◽

Jiaxing Wang ◽

Xiqing Liu

Keyword(s):

Gene Expression ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Independent Risk Factor ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Cell Renal Cell Carcinoma ◽

Low Expression

Kidney renal clear cell carcinoma (KIRC) is the most common and fatal subtype of renal cancer. Antagonistic associations between selenium and cancer have been reported in previous studies. Selenium compounds, as anti-cancer agents, have been reported and approved for clinical trials. The main active form of selenium in selenoproteins is selenocysteine (Sec). The process of Sec biosynthesis and incorporation into selenoproteins plays a significant role in biological processes, including anti-carcinogenesis. However, a comprehensive selenoprotein mRNA analysis in KIRC remains absent. In the present study, we examined all 25 selenoproteins and identified key selenoproteins, glutathione peroxidase 3 (GPX3) and type 1 iodothyronine deiodinase (DIO1), with the associated prognostic biomarker leucine-rich repeat containing 19 (LRRC19) in clear cell renal cell carcinoma cases from The Cancer Genome Atlas (TCGA) database. We performed validations for the key gene expression levels by two individual clear cell renal cell carcinoma cohorts, GSE781 and GSE6344, datasets from the Gene Expression Omnibus (GEO) database. Multivariate survival analysis demonstrated that low expression of LRRC19 was an independent risk factor for OS. Gene set enrichment analysis (GSEA) identified tyrosine metabolism, metabolic pathways, peroxisome, and fatty acid degradation as differentially enriched with the high LRRC19 expression in KIRC cases, which are involved in selenium therapy of clear cell renal cell carcinoma. In conclusion, low expression of LRRC19 was identified as an independent risk factor, which will advance our understanding concerning the selenium adjuvant therapy of clear cell renal cell carcinoma.

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