Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma - PubMed
7 hours ago
- #intratumor heterogeneity
- #immunotherapy
- #molecular classification
- The study addresses intratumor heterogeneity (ITH) in intrahepatic cholangiocarcinoma (iCCA), which hinders accurate transcriptome-based classification.
- Multi-omics analysis reveals immune and stromal heterogeneity as key drivers of ITH, causing misclassification in about 27.8% of tumors.
- A low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set is identified, leading to a new ITH-insensitive classification with five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3).
- These subgroups show distinct clinical outcomes, molecular traits, immune environments, and treatment vulnerabilities.
- Biomarkers GPRC5A and VTCN1 are robust for immunohistochemical detection of SI and SIII tumors, while serum CEA and CA19-9 help identify inflammatory iCCA.
- Therapeutically, HSP90 inhibition combined with anti-PD1 is effective for inflammatory iCCA, and anti-PD1 plus anti-TIM3 works for neurodegenerative iCCA.
- The research provides a strong molecular framework and actionable strategies for precise oncology in iCCA.