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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Malignant tumors remain a major threat to global human health. This study aimed to systematically integrate multi-omics data to identify a candidate gene with biomarker potential across diverse cancer types and to evaluate its possible clinical applications in oncology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We first performed Mendelian randomization based on summary statistics to integrate blood expression quantitative trait loci data with genome-wide association study results from esophageal adenocarcinoma, stomach cancer, and clear cell renal cell carcinoma. A comprehensive series of multi-omics bioinformatics analyses was subsequently conducted to assess the gene\u2019s expression patterns, genomic alterations, prognostic relevance, and associations with the tumor microenvironment (TME) across various cancer types. In addition, single-cell transcriptome data were analyzed to explore the gene\u2019s functional roles in the TME. The key findings were further validated through <jats:italic>in vitro<\/jats:italic> experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mendelian randomization identified peptidylprolyl isomerase H (PPIH) as a potential biomarker across multiple malignancies. Single-cell transcriptome analysis suggested that this gene may enhance the proliferative ability of malignant cells and participate in communication between immune and stromal components in the TME. Multi-omics analyses revealed that the gene is abnormally expressed and significantly correlated with patient prognosis in several cancer types. Consistently, <jats:italic>in vitro<\/jats:italic> assays demonstrated that increased expression of PPIH promotes the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study highlights PPIH as a candidate biomarker with pan-cancer relevance and potential clinical value. These findings offer new directions for cancer diagnosis and provide a foundation for further development of targeted therapeutic approaches.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1647722","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:33:51Z","timestamp":1755149631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["eQTL and multi-omics integration reveal PPIH as a prognostic and immunotherapeutic 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