Identification of Stemness Characteristics Associated With the Immune Microenvironment and Prognosis in Gastric Cancer

Abstract

BackgroundGastric cancer (GC) is a highly heterogeneous disease. In recent years, the prognostic value of the mRNA expression-based stemness index (mRNAsi) across cancers has been reported. We intended to identify stemness index-associated genes (SI-genes) for clinical characteristic, gene mutation status, immune response, and tumor microenvironment evaluation as well as risk stratification and survival prediction.MethodsThe correlations between the mRNAsi and GC prognosis, clinical characteristics, gene mutation status, immune cell infiltration and tumor microenvironment were evaluated. Weighted gene correlation network analysis (WGCNA) was performed to identify SI-genes from differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA). Single-sample gene set enrichment analysis (ssGSEA) was employed to calculate the sample SI-gene-based ssGSEA score according to the SI-genes. Then, the correlations between the ssGSEA score and GC prognosis, clinical characteristics, gene mutation status, immune cell infiltration and tumor microenvironment were analyzed. Finally, the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to construct a prognostic signature with prognostic SI-genes. The ssGSEA score and prognostic signature were validated using the Gene Expression Omnibus (GEO) database.ResultsThe mRNAsi could predict overall survival (OS), clinical characteristics, the gene mutation status, immune cell infiltration, and the tumor microenvironment composition. Fourteen positive SI-genes and 178 negative SI-genes were screened out using WGCNA. The ssGSEA score, similar to the mRNAsi, was found to be closely related to OS, clinical characteristics, the gene mutation status, immune cell infiltration, and the tumor microenvironment composition. Finally, a prognostic signature based on 18 prognostic SI-genes was verified to more accurately predict GC 1-year, 3-year, and 5-year OS than traditional clinical prediction models.ConclusionThe ssGSEA score and prognostic signature based on 18 prognostic SI-genes are of great value for immune response evaluation, risk stratification and survival prediction in GC and suggest that stemness features are crucial drivers of GC progression.

Integrative Analysis of Biomarkers Through Machine Learning Identifies Stemness Features in Colorectal Cancer

“…Moreover, we found that immune score was lower in the high-mRNAsi group than in the low-mRNAsi group for both colon and rectal cancer (Wilcoxon rank sum test, p < 0.001, Figures 2D,G ). Moreover, immune score has been proven lower in the high-mRNAsi group than in the low-mRNAsi group for gastric cancer ( Mao et al, 2021 ). In addition, when comparing the tumor mutational burden (TMB) in groups with different levels of stemness index, we observed the opposite trend, with the level of TMB increasing from the low-mRNAsi group to the high-mRNAsi group (low mRNAsi < high mRNAsi) (Wilcoxon rank sum test, p < 0.001, Figures 2E,H ).…”

“…The mRNAsi of colon and rectal cancer tissues was significantly higher than that of normal tissues (Wilcoxon rank sum test, p < 0.05, Figures 1A,H), which suggested that the level of stemness is associated with tumor development. The mRNAsi among different stages of colon and rectal cancer did not show significant differences (Mann-Whitney U-test, p < 0.05, Figures 1B,C,I,J), which suggested the mRNAsi may not be closely related to the clinical stage in many tumor types (Bai et al, 2020;Mao et al, 2021;Pei et al, 2020). In our study, the colon and rectal cancer patients were divided into high-mRNAsi and lowmRNAsi groups based on the cutoff value determined by the median mRNAsi index (Figures 1D-G,K-N).…”

Integrated Analysis of Stemness-Related LncRNAs Helps Predict the Immunotherapy Responsiveness of Gastric Cancer Patients

“…Numerous studies have been reported to investigate whether tumor immune microenvironment could be affected by stemness features. Mao et al (2021) developed a mRNA expression-based stemness index system based on weighted gene correlation network analysis to reveal that the stemness index indicated a distinct immune spectrum. Alex et al used gene expression-based metrics to evaluate the association of stemness with immune cell infiltration and genomic, transcriptomic, and clinical parameters across 21 solid cancers.…”

Cross-Talk of Focal Adhesion-Related Gene Defines Prognosis and the Immune Microenvironment in Gastric Cancer

“…Here, whether there is an association between the focal adhesion mutation and mRNAsi, our results show that the mRNAsi of patients with mutations is significantly higher than that of patients without mutations (P < 0.0001) (Supplementary Figure 1B). The previous study (Mao et al, 2021) has reported that patients with high mRNAsi have a better prognosis. In terms of prognosis, the results of this study are consistent with them.…”

“…The mRNA expression-based stemness index (mRNAsi) of GC was reported by Malta et al (2018). TMB of GC was extracted according to the method we reported before (Mao et al, 2021). The focal adhesion-related genes (Supplementary…”