Comprehensive analysis of transcriptome data stemness indices identifies key genes for controlling cancer stem cell characteristics in gastric cancer.

Abstract

BackgroundCancer stem cells (CSCs) are the tumor cell of origin with self-renewing ability and multi-differentiation potency. CSCs can play vital roles in gastric cancer (GC) metastasis and relapse. However, the genes that regulate the stemness maintenance of CSCs in GC patients remain largely unknown. In the present study, we sought to determine the key genes associated with stemness in GC patients.MethodsmRNA expression-based stemness index (mRNA SI) was analyzed with regard to the differential expression levels between normal and GC tissues, as well as clinical features and survival outcomes. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules of interest and key genes. The differences in mRNA expression of key genes between normal and GC tissues were calculated by “ggpubr” package in R. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were carried out to annotate the function of key genes. Protein-protein interaction (PPI) and gene co-expression analyses were conducted using STRING and “corrplot” package in R, respectively.ResultsmRNA SI score was markedly increased in GC tumor compared to normal tissues. High mRNA SI score was remarkably associated with more advanced tumor stage and higher pathologic grade, but longer survival times. Based on the results of WGCNA, 19 key genes (i.e., BUB1, BUB1B, KIF14, NCAPH, RACGAP1, KIF15, CENPF, TPX2, RAD54L, KIF18B, TTX, KIF4A, SGO2, PLK4, ARHGAP11A, XRCC2, C1orf112, NCAPG, ORC6) were identified. GO and KEGG functional analyses revealed that these 19 key genes were mainly related to cell proliferation. From PPI and gene co-expression analyses, these 19 key genes were discovered to be intensively associated with each other at both protein and transcription levels.Conclusionsour study identified 19 key genes that play vital roles in the stemness maintenance of CSCs in GC patients. Targeting these key genes may help to control CSC characteristics in GC.