An integrative approach identified genes associated with drug response in gastric cancer

Carcinogenesis
Jin ZhouLiang Kee Goh

Abstract

Gastric cancer (GC) is the second leading cause of global cancer mortality worldwide. However, the molecular mechanism underlying its carcinogenesis and drug resistance is not well understood. To identify novel functionally important genes that were differentially expressed due to combinations of genetic and epigenetic changes, we analyzed datasets containing genome-wide mRNA expression, DNA copy number alterations and DNA methylation status from 154 primary GC samples and 47 matched non-neoplastic mucosa tissues from Asian patients. We used concepts of 'within' and 'between' statistical analysis to compare the difference between tumors and controls within each platform, and assessed the correlations between platforms. This 'multi-regulated gene (MRG)' analysis identified 126 differentially expressed genes that underwent a combination of copy number and DNA methylation changes. Most genes were located at genomic loci associated with GC. Statistical enrichment analysis showed that MRGs were enriched for cancer, GC and drug response. We analysed several MRGs that previously had not been associated with GC. Knockdown of DDX27, TH1L or IDH3G sensitized cells to epirubicin or cisplatin, and knockdown of RAI14 reduced cell proliferat...Continue Reading

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Citations

Jan 27, 2017·Journal of the National Cancer Institute·Wanpei CaiAlan Prem Kumar
Feb 6, 2020·Journal of Clinical Medicine·Lara CostantiniNicolò Merendino
Dec 3, 2021·Technology in Cancer Research & Treatment·Wang XiaoqianZheng Peng

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