Identification of the hub genes and prognostic indicators of gastric cancer and correlation of indicators with tumor-infiltrating immune cell levels

J Cancer. 2021 May 13;12(13):4025-4038. doi: 10.7150/jca.52105. eCollection 2021.

Abstract

Aims: To identify the hub genes and prognostic indicators of gastric cancer (GC) and determine the correlation between prognostic indicators and the tumor-infiltrating immune cell levels so as to provide useful information for future GC diagnosis and treatment. Methods: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma dataset and two microarray datasets were used to screen the overlapping differentially expressed genes (DEGs) between normal gastric and GC tissue samples. Hub genes were screened via protein-protein interaction networks and module analysis of the overlapping DEGs. Their expression was validated at the cell level and tissue level using the ONCOMINE database. The prognostic indicators of overall survival (OS) and disease-free survival was identified by Cox proportional hazards regression analysis based on tumor grade and cancer stage. The expression of hub genes was validated at the cell level. The correlation of prognostic indicators with the tumor-infiltrating immune cell levels was analyzed using Tumor IMmune Estimation Resource. Results: Ten hub genes, namely CDC6, CDC20, BUB1B, TOP2A, CDK1, AURKA, CCNA2, CCNB1, MAD2L1, and KIF11, were screened and their upregulation in the GC tissue was verified. Three prognostic factors, namely LUM, VCAN, and EFNA4, were identified; their expression was higher in GC cells than in normal cells. LUM, VCAN, and EFNA4 were correlated with tumor-infiltrating immune cell levels in GC. Significance: The identified hub genes and prognostic indicators of GC could be useful indicators for future GC diagnosis and treatment.

Keywords: Hub gene; differentially expressed genes; gastric cancer; prognostic indicators; tumor-infiltrating immune cells.