Identification of specific modules and hub genes associated with the progression of gastric cancer

• Published in: Carcinogenesis (New York) 2019-10, Vol.40 (10), p.1269-1277
• Main Authors: Gong, Congcong, Hu, Yang, Zhou, Mao, Yao, Maojin, Ning, Zhengxiang, Wang, Zhi, Ren, Jiaoyan
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers, Tumor - genetics; Case-Control Studies; Cell Proliferation; Computational Biology; Disease Progression; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; MicroRNAs - genetics; Prognosis; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Survival Rate; Transcriptome; Tumor Cells, Cultured
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgz040

Abstract Gastric cancer (GC) has high morbidity and mortality rates worldwide. Abundant literature has reported several individual genes and their related pathways intimately involved in tumor progression. However, little is known about GC progression at the gene network level. Therefore, understanding the underlying mechanisms of pathological transition from early stage to late stage is urgently needed. This study aims to identify potential vital genes and modules involved in the progression of GC. To understand the gene regulatory network of GC progression, we analyzed micro RNAs and messenger RNA s expression profiles by using a couple of bioinformatics tools. miR-205 was identified by differentially expressed analysis and was further confirmed through using multiple kernel learning-based Kronecker regularized least squares. Using weighted gene co-expression network analysis, the gastric cancer progression-related module, which has the highest correlation value with cancer progression, was obtained. Kyoto Encyclopedia of Genes and Genomes pathways and biological processes of the GCPR module genes were related to cell adhesion. Meanwhile, large-scale genes of GCPR module were found to be targeted by miR-205, including two hub genes SORBS1 and LPAR1. In brief, through multiple analytical methods, we found that miR-205 and the GCPR module play critical roles in GC progression. In addition, miR-205 might maintain cell adhesion by regulating SORBS1 and LPAR1. To screen the potential drug candidates, the gene expression profile of the GCPR module was mapped connectivity map (Cmap), and the mTOR inhibitor (Sirolimus) was found to be the most promising candidate. We further confirmed that Sirolimus can suppress cell proliferation of GC cell in vitro. This study identified miR-205 and its target module [the gastric cancer progression-related module (GCPR)] intimately involved in gastric cancer (GC) progression by multimethods analysis. Using the GCPR module, we obtained the mTOR inhibitor Sirolimus as the drug candidate for GC.