Identification and Validation of the Hub Genes in Gastric Cancer Through Weighted Gene Co-Expression Network Analysis

Abstract

Background: Gastric cancer is one of the most lethal tumors and is characterized by poor prognosis and lack of effective diagnostic or therapeutic biomarkers. The aim of this study was to find hub genes serving as biomarkers in gastric cancer diagnosis and therapy. Methods: GSE66229 from Gene Expression Omnibus (GEO) was used as training set. Genes bearing the top 25% standard deviations among all the samples in training set were performed to systematic weighted gene co-expression network analysis (WGCNA) to find candidate genes. Then, hub genes were further screened by using the “least absolute shrinkage and selection operator” (LASSO) logistic regression. Finally, hub genes were validated in GS54129 dataset from GEO by supervised learning methods logistic regression algorithms.Results: 12 modules with strong preservation were identified by using WGCNA methods in training set. Of which, two modules significantly related to gastric cancer were selected as clinically significant modules, and 43 candidate genes were identified from these two modules. Then, ACADL, ADIPOQ, ARHGAP39, ATAD3A, C1orf95, CCKBR, GRIK3, SCNN1G, SIGLEC11, and TXLNB were screened as the hub genes. These hub genes successfully differentiated the tumor samples from the healthy tissues in an independent testing set through the logistic regression algorithm, with the area under the receiver operating characteristic curve at 0.882. Conclusions: These hub genes bearing diagnostic and therapeutic values, and our results may provide a novel prospect for the diagnosis and treatment of gastric cancer in the future.

Mechanistic of Rac and Cdc42 synchronization at the cell edge by ARHGAP39-dependent signaling nodules and the impact on protrusion dynamics

“…Because GAPs inhibit GTPase activity, it is legitimate that GAPs that are frequently inactivated or downregulated in human cancers are considered as tumor suppressors (Vigil et al, 2010) as DLC1 (deleted in liver cancer, known also as ARHGAP7) (Xue et al, 2008;Yuan et al, 1998) or GRAF (GTPase regulator associated with focal adhesion kinase-1, known also as ARHGAP26) (Borkhardt et al, 2000;Hildebrand et al, 1996;Yao et al, 2015). In contrast, ARHGAP39 gene is upregulated in most human cancers in the Cancer Genome Atlas (TCGA) database, its high expression level is associated with poor survival (http://www.oncolnc.org) and might be considered as a potential marker for gastric cancer (Li et al, 2021). Depletion of ARHGAP39 in cells or expression of GAP inactive ARHGAP39 significantly reduces cell invasion in vitro and in mice.…”