Pan-cancer analysis and experimental validation identify CYP19A1 as a prognostic biomarker and oncogenic driver associated with tumor immune microenvironment regulation in gastrointestinal cancers

CYP19A1, which encodes the enzyme aromatase necessary for estrogen production, is known to be involved in hormone-sensitive cancers, but its role in gastrointestinal cancers is not completely clear. To examine CYP19A1 in gastrointestinal cancers, we carried out pan-cancer bioinformatics analyses using the TCGA dataset as the main source, combined with experimental validations. A systematic analysis was conducted on transcriptomic, clinical, epigenetic, immune infiltration data, functional networks, and regulatory mechanisms. Functional experiments were conducted using mouse models of gastric and colon cancer, as well as human cancer cell lines such as AGS, MKN45, SGC7901, HCT116, SW480, and LoVo. Higher levels of CYP19A1 expression are found in stomach, liver, and colon cancers, which are associated with more advanced stages and poorer prognosis. The increase in its expression may be related to immune profiles specific to certain cancer types and might help create an immunosuppressive tumor microenvironment in gastrointestinal cancers, as shown by immune infiltration analysis. GO and KEGG enrichment analyses suggest that CYP19A1 is linked to pathways involved in steroid hormone synthesis, cancer-related signaling, and endocrine resistance, indicating its role in the progression of hormone-driven cancers. Functional tests indicated that higher CYP19A1 expression enhanced cancer cell migration and invasion, whereas lowering it produced the opposite outcome. The combined computational and experimental findings identify CYP19A1 as a prognostic biomarker and a functional contributor to gastrointestinal cancers. The results support exploring CYP19A1-specific treatments, including aromatase inhibitors and immune-modulating tactics, in this cancer group with a considerable burden.