Abstract
Background: Gastric cancer (GC) is a highly heterogeneous and complex disease. Recent evidence has shown that members of the Integrin β superfamily (ITGBs) play crucial roles in the initiation and progression of various types of human cancer. However, the specific role and mechanism of ITGB1, one of the representative factors within the integrin family, in GC have not been fully elucidated.
Methods: The study systematically analysed the expression and prognostic significance of ITGBs in pan-cancer using data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx). Multivariate regression analysis was used to identify the key factors that influence the prognosis of GC. Noncoding RNAs (ncRNAs) that contribute to ITGB1 expression were subsequently identified through a combination of in silico analyses, including expression, correlation, and survival analysis. The relationship between ITGB1 and its lncRNA MIR99AHG expression with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in GC was then elucidated.
Results: Compared to the adjacent normal tissue, the results show a significant increase in ITGB1-2 and ITGB4-8 mRNA levels in GC. Cox regression and Kaplan-Meier survival analyses indicate that elevated expression of ITGB1 is associated with a poor prognosis and can serve as an independent prognostic factor in GC patients. The MIR99AHG/hsa-mir-17-5p axis has been identified as the most promising upstream ncRNA-related pathway involved in regulating ITGB1 expression in GC through comprehensive expression analysis, correlation analysis, and survival analysis. Additionally, the expressions of both ITGB1 and MIR99AHG have been validated through immunohistochemical analysis using our collection of GC tissues. Finally, our study shows a positive correlation between the levels of infiltrating CD4+ T cells, macrophages, and dendritic cells, and the expression of ITGB1. High levels of macrophages are particularly indicative of a better prognosis in GC.
Conclusion: Our findings suggest that ncRNAs-mediated ITGB1 expression is associated with poor prognosis and tumor immune infiltration in GC. However, it is necessary to conduct further validation through extensive basic experiments and large-scale clinical trials in the future.