Work

Integrated multi-omics analysis of prognostic model and immune microenvironment in intrahepatic cholangiocarcinoma

Year: 2026

Type: article

Abstract: • This study constructed a single-cell atlas of iCCA, identifying tumor-specific SPP1⁺ macrophage and NDRG1⁺ CAF as key cellular components. • This study created the prognostic model of SPP1⁺ macrophage and NDRG1⁺ CAF through 10 machine learning algorithms. • This study revealed specific cell-cell interaction, potentially regulated by inflammation promoting may promote an immune-excluded phenotype that limits T-cell infiltration. • This study highlights the MT1X as a potential therapeutic target to iCCA treatment. Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy originating from the epithelial lining of second-order bile ducts. Despite advances in immunotherapy, which underscore the pivotal roles of T-cell dynamics and tumor microenvironment (TME) remodeling in anti-tumor immunity, iCCA remains a clinical challenge due to its rapid progression. Consequently, there is a pressing need for integrated multi-omics approaches to elucidate the immune landscape of iCCA and guide effective precision immunotherapy. To comprehensively characterize iCCA, we integrated single-cell RNA-seq data for microenvironment analysis and bulk RNA-seq cohorts for prognostic model construction using machine learning, followed by external validation and functional experimental verification of key genes. Integrated single-cell and spatial transcriptomic analysis of iCCA uncovered interacting epithelial-fibroblast subpopulations and guided the machine learning-based derivation of a five-gene prognostic signature. Furthermore, spatial transcriptomics confirmed the physical co-localization between SPP1+ Macrophage and NDRG1+ CAF. Finally, functional experiments established that MT1X, a gene highly expressed in iCCA, drives tumor proliferation, migration, and invasion. This study establishes a prognostic model based on five key genes and elucidates their role in the immunosuppressive TME. MT1X was validated as a pro-tumorigenic factor, highlighting its potential as a therapeutic target.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2026.102675