ArticleBMC cancer2026
Integrated DNA and RNA profiling refines prognostic stratification independent of therapeutic actionability in cholangiocarcinoma.
Article in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCholangiocarcinoma (CCA) exhibits marked biological heterogeneity. While genomic profiling identifies targetable alterations such as FGFR2 fusions and IDH1 mutations, transcriptomic analyses reveal distinct immune, proliferative and mesenchymal profiles. How these genomic and transcriptomic features jointly influence clinical outcomes remains unclear.
methodsWe performed integrated DNA and RNA profiling in 62 patients with intrahepatic and extrahepatic CCA treated at a single tertiary center. Targeted DNA sequencing assessed single-nucleotide variants, copy-number alterations, and microsatellite instability. Extended RNA sequencing evaluated gene fusions and pathway-level transcriptomic subtypes. Associations with progression-free survival (PFS) and overall survival (OS) were examined.
resultsAmong 58 DNA-profiled tumors, the most frequent alterations were TP53 (43.1%) and KRAS (29.3%), followed by IDH1 (10.3%, restricted to intrahepatic CCA). Actionable alterations (IDH1, FGFR2 fusions, ERBB2 amplification, microsatellite instability-high) were detected in 25% of cases and associated with longer overall survival (67.5 vs. 20.8 months; p = 0.0004), consistent with benefit from matched therapies rather than intrinsic tumor biology. RNA profiling identified five transcriptomic subtypes: Immune (21%), Proliferative (18%), Mesenchymal (42%), Immune-Proliferative (8%), and Unclassified (11%). KRAS-TP53 co-mutation was the strongest adverse prognostic factor (38.1 vs. 13.2 months; p = 0.0004). The Mesenchymal subtype was associated with shorter PFS (5.9 vs. 17.9 months; p = 0.045) in patients treated with chemotherapy ± immunotherapy but did not significantly affect OS.
conclusionsIntegrated genomic and transcriptomic profiling refines prognostic stratification in cholangiocarcinoma independent of therapeutic actionability. KRAS-TP53 co-mutation and the Mesenchymal transcriptomic subtype represent independent high-risk markers detectable on routine FFPE tissue. These features complement actionable alterations and may inform patient selection and clinical trial design.
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