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

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.

Gene Expression Network Analysis of Precursor Lesions in Familial Pancreatic Cancer

“…6 The application of WGCNA to identify gene expression networks potentially involved in crucial molecular pathways for progression of cancer is becoming an increasingly prevalent area in oncogenomic studies among different types of high-morbidity cancers, including breast cancer, colon cancer, gastric cancer, and pancreatic cancer. [7][8][9][10] Implementation of WGCNA on genomic data on FPC could open new perspectives for the characterization of hereditary pancreatic cancer-identifying important pathways and hub genes associated with molecular mechanisms in the progression of FPC.…”

Identification and Validation of CYBB, CD86, and C3AR1 as the Key Genes Related to Macrophage Infiltration of Gastric Cancer

“…Another study aimed to identify potential vital miRNAs and modules associated with the progression of GC (Gong et al, 2019). Our study revealed the important genes and pathways associated with macrophages in GC for the first time.…”

A New Prognostic Risk Model Based on PPAR Pathway-Related Genes in Kidney Renal Clear Cell Carcinoma

“…SORBS1, also known as Cap/Ponsin protein, can regulate biological processes such as growth factor signaling, cell adhesion, and cancer metastasis [ 61 ]. The primary function of the protein encoded by PLTP is to transfer phospholipids from triglyceride-rich lipoproteins to high-density lipoproteins.…”