Cancer constitutes a significant global health challenge, contributing to escalating socioeconomic burdens and necessitating the urgent identification of novel biomarkers and therapeutic targets. This study seeks to investigate the expression levels of integrin α3 (ITGA3) across various cancer types and its association with immune cell infiltration, thereby elucidating its potential role in cancer progression at the pan-cancer level. By employing expression profile data from The Cancer Genome Atlas (TCGA) and supplementary data from the Human Protein Atlas (HPA), we performed differential expression analysis, single-cell RNA expression analysis, Western blotting, immunohistochemical analysis, and subcellular immunofluorescence staining analysis to evaluate the expression levels and patterns of ITGA3 in diverse cancer types. Utilizing mutation analysis from cBioPortal, functional enrichment, and protein–protein interaction analysis from the STRING database, alongside six advanced immune cell abundance estimation algorithms—TIMER, xCell, MCP-counter, CIBERSORT, EPIC, and quanTIseq—we identified that ITGA3 exhibits differential expression across various cancer types. This expression is correlated with numerous clinical features, immune cell infiltration, immunotherapy response, and mutation burden, ultimately influencing patient prognosis. These findings underscore the potential regulatory role of ITGA3 within the tumor microenvironment and offer novel insights into its potential as a biomarker and therapeutic target in immunotherapy at the pan-cancer level. Future studies should verify the specific mechanisms of ITGA3 in cancer progression and the immune microenvironment.
Supplementary Information: The online version contains supplementary material available at 10.1007/s12672-025-03944-8.
Keywords: ITGA3; Immune infiltration; Pan-cancer; Prognosis.