ITGA11, a Prognostic Factor Associated with Immunity in Gastric Adenocarcinoma.

BACKGROUND: Stomach adenocarcinoma (STAD) presents a challenge given its advanced stage at diagnosis and poor prognosis. Integrin subunit alpha 11 (ITGA11) encodes alpha integrin and has been implicated in promoting tumorigenesis and development by participating in cell proliferation and invasion. However, the precise mechanism of ITGA11 in STAD remains unclear.

METHODS: The differences in ITGA11 expression levels between 375 gastric cancer samples and 32 paracancerous tissue samples from the Cancer Genome Atlas (TCGA) database were examined. The relationship between ITGA11 expression and clinical features and ITGA11 diagnostic and prognostic value were evaluated using the chi-square test and receiver operating characteristic (ROC) assay. Differentially expressed genes were identified based on ITGA11 expression. Subsequently, functional enrichment analyses were conducted using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Furthermore, immune infiltration and the expression of ITGA11-associated immune checkpoints in patients with tumors were assessed using CIBERSORT, single-sample gene set enrichment analysis, and the TIMER database. Drug sensitivity associated with ITGA11 expression was analyzed using the R oncoPredict package to guide treatment decisions. Finally, the difference in ITGA11 expression between cancer tissue and the adjacent tissues was validated using quantitative PCR (qPCR) and immunohistochemistry.

RESULTS: The gastric cancer tissue had significantly upregulated ITGA11 expression compared to paracancerous tissues. ITGA11 demonstrated robust diagnostic and prognostic value in gastric cancer (GC) and was an independent risk factor for adverse outcomes. The patients with STAD with elevated ITGA11 expression levels had heightened immune cell infiltration and increased immune checkpoint marker expression. Notably, patients with increased ITGA11 expression demonstrated reduced responsiveness to oxaliplatin and afatinib.

CONCLUSION: The results indicated the pivotal role of ITGA11 in shaping the tumor immune microenvironment, ultimately establishing ITGA11 as an immune-related prognostic predictor within the intricate landscape of STAD.