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Solid Tumors / Tumor Microenvironment / Tumor Immune Microenvironment · Journal article
Cancer Biology & Therapy · July 14, 2026
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This retrospective multi-omics analysis characterizes PI4K/PIPK genomic alterations across 18 solid tumor types in 2,144 Chinese patients, identifying PI4K2B amplification as a potential prognostic biomarker in colorectal cancer. The study reveals tissue-specific immune landscapes and associations with tumor mutational burden and microsatellite instability, providing an exploratory framework for future precision oncology strategies.
Retrospective multi-omics analysis. 2,144 Chinese patients with 18 solid tumor types. n = 2,144.
PI4K/PIPK alterations were identified in 10.5% of 2,144 patients, with PIP4K2C amplification reaching 48% PI4K2B amplification and overexpression are consistently associated with poor prognosis in COAD Alterations significantly correlated with higher TMB and MSI-H status
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PI4K2B may serve as a prognostic biomarker in colorectal cancer, with potential clinical utility analogous to HER2. The heterogeneous effects across cancers suggest tissue-specific evaluation is necessary before clinical stratification.
Exploratory retrospective analysis identifying genomic alteration patterns and associations, requiring prospective validation before clinical implementation.
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PI4K2B may serve as a prognostic biomarker in colorectal cancer, with potential clinical utility analogous to HER2. The heterogeneous effects across cancers suggest tissue-specific evaluation is necessary before clinical stratification.
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Background. This study aimed to systematically characterize the genomic alteration landscape of phosphatidylinositol 4-kinase (PI4K) and phosphatidylinositol phosphate kinase (PIPK) family genes in solid tumors, assess the correlation of these alterations with patient clinical outcomes and the tumor immune microenvironment, and explore their potential as novel biomarkers or therapeutic targets.Methods. A retrospective analysis was conducted on whole-exome sequencing data from a cohort of 2,144 Chinese patients encompassing 18 solid tumor types. Genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) pan-cancer project were integrated to perform survival analysis, correlating genomic alterations, gene expression levels, and patient overall survival. Associations between these gene alterations and tumor mutational burden (TMB), microsatellite instability (MSI), and levels of tumor-infiltrating immune cells were also evaluated.Results. We identified PI4K/PIPK alterations in 10.5% of 2,144 patients, with PIP4K2C amplification reaching 48%. While PI4K2B amplification and overexpression are consistently associated with poor prognosis in COAD, family-wide effects were highly heterogeneous across cancers. Alterations significantly correlated with higher TMB and MSI-H, and multi-omics analysis revealed tissue-specific immune landscapes, highlighting the family's potential for risk stratification and immunotherapy.Conclusions. This study provides the first systematic delineation of the genomic alteration landscape of PI4K and PIPK families at a pan-cancer scale within a Chinese population. It identifies PI4K2B as an amplification-driven prognostic biomarker in colorectal cancer, with potential clinical value analogous to HER2. These findings illuminate the significant roles of these kinases in cancer and provide novel insights for future precision oncology strategies.
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