FKBP10 as a prognostic biomarker and therapeutic target in hepatocellular carcinoma.

[BACKGROUND] Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited treatment options and poor prognosis. FK506-binding protein 10 (FKBP10), a member of the FKBP family, has been associated with the progression of various cancers, but its role in HCC remains unclear.

[METHODOLOGY] In this study, we performed a comprehensive multi-omics analysis integrating bulk and single-cell transcriptomic data to investigate the expression pattern, clinical relevance, immune landscape, and functional roles of FKBP10 in HCC. Public datasets including TCGA, CPTAC, GEPIA, TIMER, and TISIDB were used for transcriptomic and clinical correlation analyses.

[RESULTS] Our findings showed that gene enrichment and gene set enrichment analysis (GSEA) revealed that FKBP10 is involved in extracellular matrix (ECM) organization and epithelial-mesenchymal transition (EMT). Single-cell and spatial transcriptomics identified FKBP10 as a specific marker of cancer-associated fibroblasts (CAFs), which displayed strong intercellular signaling through collagen and laminin pathways. High FKBP10 expression was significantly associated with advanced tumor grade, lymph node metastasis, and HBV infection, and served as an independent predictor of poor overall and disease-free survival. Furthermore, FKBP10 expression correlated with an immunosuppressive tumor microenvironment and elevated expression of immune checkpoint genes. Drug sensitivity profiling indicated that tumors with high FKBP10 expression may be more responsive to PI3K-mTOR and AKT inhibitors.

[CONCLUSION] These findings suggest that FKBP10 plays a multifaceted role in HCC progression and may serve as both a prognostic biomarker and a potential therapeutic target.