Identification of the hub genes in gastric cancer through weighted gene co-expression network analysis

PeerJ. 2021 Mar 5:9:e10682. doi: 10.7717/peerj.10682. eCollection 2021.

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 the GSE54129 dataset from GEO by supervised learning method artificial neural network (ANN) algorithm.

Results: Twelve modules with strong preservation were identified by using WGCNA methods in training set. Of which, five modules significantly related to gastric cancer were selected as clinically significant modules, and 713 candidate genes were identified from these five modules. Then, ADIPOQ, ARHGAP39, ATAD3A, C1orf95, CWH43, GRIK3, INHBA, RDH12, SCNN1G, SIGLEC11 and LYVE1 were screened as the hub genes. These hub genes successfully differentiated the tumor samples from the healthy tissues in an independent testing set through artificial neural network algorithm with the area under the receiver operating characteristic curve at 0.946.

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.

Keywords: Gastric cancer; LASSO regression; Supervised machine learning; WGCNA; Weighted gene co-expression network analysis.

Grants and funding

This work was supported by the Science & Technology Department of Sichuan Province funding project (No. 2016FZ0108, 2017FZ0104), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC18010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.