Identification of the key genes controlling stomach adenocarcinoma stem cell characteristics via an analysis of stemness indices

Guangwen Wang; Zhenhua Wu; Yesheng Huang; Yingbang Li; Yunpeng Bai; Zhidan Luo; Wendong Huang; Zanxiong Chen

doi:10.21037/jgo-22-244

Identification of the key genes controlling stomach adenocarcinoma stem cell characteristics via an analysis of stemness indices

J Gastrointest Oncol. 2022 Apr;13(2):593-604. doi: 10.21037/jgo-22-244.

Authors

Guangwen Wang^#¹, Zhenhua Wu^#², Yesheng Huang^#², Yingbang Li¹, Yunpeng Bai¹, Zhidan Luo¹, Wendong Huang¹, Zanxiong Chen³

Affiliations

¹ Center of Scientific Research, Maoming People's Hospital, Maoming, China.
² Department of Gastroenterology, Maoming People's Hospital, Maoming, China.
³ Office of Maoming People's Hospital, Maoming People's Hospital, Maoming, China.

^# Contributed equally.

Abstract

Background: In-depth research on tumors has shown that cancer stem cells (CSCs) play a crucial role in tumorigenesis. However, the mechanisms underlying the growth and maintenance of CSCs in stomach adenocarcinoma (STAD) are unclear. This study sought to investigate the expression of stem cell-related genes in STAD.

Methods: We identified key genes related to STAD stem cell characteristics by combining gene expression data obtained from The Cancer Genome Atlas to define a messenger ribonucleic acid expression-based stemness index (mRNAsi) based on mRNA expression. The correlations between the mRNAsi and STAD clinical characteristics, including age, tumor grade, pathological stage, and survival status, were explored. Additionally, a weighted gene co-expression network analysis was conducted to identify relevant modules and key genes. The expression verification and functional analysis of the key genes was carried out using multiple databases, including the TIMER (https://cistrome.shinyapps.io/timer/), and Gene Expression Profiling Integrative Analysis, and Gene Expression Omnibus databases.

Results: The mRNAsi score was closely related to the clinical characteristics of STAD, including age, tumor grade, pathological stage, and survival status. Similarly, the mRNAsi score was significantly higher in STAD tissues than normal tissues, and the score decreased with tumor stage. The higher the mRNAsi score, the higher the overall survival rate. We screened a module of interest and found a strong correlation between 19 key genes. Among these 19 key genes, 16 had previously been shown to be closely related to STAD survival. The functional analysis showed that these key genes were linked to cell-cycle events, such as chromosome separation, mitosis, and microtubule movement.

Conclusions: We identified 19 key genes that play an important role in the maintenance of STAD stem cells. Among these genes, 16 play a role in predicting the prognosis of STAD patients. The cell-cycle pathway was the most important signaling pathway for the key genes associated with STAD stem cells. These findings may provide a new rationale for screening therapeutic targets and the characterization of STAD stem cells.

Keywords: Stomach adenocarcinoma (STAD); WGCNA; cancer cell stemness; mRNAsi.