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

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.

Correlation between chromatin epigenetic-related lncRNA signature (CELncSig) and prognosis, immune microenvironment, and immunotherapy in non-small cell lung cancer

“…Also, mRNAsi is closely associated with various clinical characteristics. Prior studies suggest that altered expression of mRNAsi in tissue can serve as a biomarker for identifying differentially expressed genes in cancer prognosis research [ 35 , 45 ].…”

“…Stemness Indices is an index that describes the similarity of cancer cells to stem cells and can be used as a prognostic indicator to predict the risk of tumor recurrence and guide treatment [ 34 ]. By using a one-class logistic regression (OCLR) algorithm to train the tumor stem cell (ESC, embryonic stem cell; iPSC, induced pluripotent stem cell) classes and their differentiated ectoderm, mesoderm, and endoderm progenitors, then applied to The Cancer Genome Atlas (TCGA) dataset to calculate the mRNA gene expression-based stemness index (mRNAsi) [ 35 ]. Our index of mRNA expression of lung cancer stem cells is based on the available data [ 34 ].…”