Identification of key genes controlling cancer stem cell characteristics in gastric cancer

Chao Huang; Ce-Gui Hu; Zhi-Kun Ning; Jun Huang; Zheng-Ming Zhu

doi:10.4240/wjgs.v12.i11.442

Identification of key genes controlling cancer stem cell characteristics in gastric cancer

World J Gastrointest Surg. 2020 Nov 27;12(11):442-459. doi: 10.4240/wjgs.v12.i11.442.

Authors

Chao Huang¹, Ce-Gui Hu¹, Zhi-Kun Ning¹, Jun Huang¹, Zheng-Ming Zhu²

Affiliations

¹ Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
² Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China. zzm8654@163.com.

Abstract

Background: Self-renewal of gastric cancer stem cells (GCSCs) is considered to be the underlying cause of the metastasis, drug resistance, and recurrence of gastric cancer (GC).

Aim: To characterize the expression of stem cell-related genes in GC.

Methods: RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database, and the results of the GC mRNA expression-based stemness index (mRNAsi) were analyzed. Weighted gene coexpression network analysis was then used to find modules of interest and their key genes. Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter, and the online database Oncomine was used to assess the expression of key genes in GC.

Results: mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues (P < 0.0001). A total of 16 modules were obtained from the gene coexpression network; the brown module was most positively correlated with mRNAsi. Sixteen key genes (BUB1, BUB1B, NCAPH, KIF14, RACGAP1, RAD54L, TPX2, KIF15, KIF18B, CENPF, TTK, KIF4A, SGOL2, PLK4, XRCC2, and C1orf112) were identified in the brown module. The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component, the sister chromatid segregation biological process, the motor activity molecular function, and the cell cycle and homologous recombination pathways. Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes (RAD54L, TPX2, and XRCC2) were consistently related.

Conclusion: Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics. RAD54L, TPX2, and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.

Keywords: Cancer stem cell; Gastric cancer; Key gene; The Cancer Genome Atlas database; Weighted gene coexpression network analysis; mRNA expression-based stemness index.