Multi-Omics Integration Identifies a Molecular Subtype of Intrahepatic Cholangiocarcinoma with Enhanced Benefit from Adjuvant Therapy - PubMed
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- #Adjuvant therapy biomarkers
- #Intrahepatic cholangiocarcinoma
- #Multi-omics analysis
- Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous liver cancer with poor prognosis, requiring better stratification for postoperative therapy guidance.
- Integrative multi-omics analysis (using datasets like FU-iCCA Cohort and GSE244807) defined three robust molecular subtypes of iCCA with distinct genomic alterations, pathway activation, immune microenvironments, and overall survival differences.
- Eight marker genes distinguishing the subtypes were prioritized via protein-protein interaction network analysis and consensus feature selection.
- A Cox proportional-hazards model based on these markers stratified patients into high- and low-risk groups, with high-risk iCCA characterized by elevated expression of CLDN18, MUC1, and MUC5AC and worse OS without adjuvant therapy.
- In an independent validation cohort of 174 resected iCCA patients, high expression of CLDN18, MUC1, or MUC5AC was associated with markedly prolonged OS in those receiving adjuvant chemotherapy or chemoembolization, compared to untreated patients.
- Marker-negative patients showed no clear benefit from adjuvant therapy.
- The study identifies a high-risk, mucin-enriched subtype of iCCA, with CLDN18, MUC1, and MUC5AC as candidate predictive biomarkers for adjuvant chemotherapy benefit, warranting prospective validation.