Integrative Genomic and Clinical Profiling of Colorectal Cancer Liver Metastases to Guide Personalized Surgery and Liver Transplantation.

Colorectal cancer liver metastases (CRLM) remain a leading cause of cancer-related mortality. Although hepatic resection is the only established curative option, recurrence exceeds 60%, underscoring substantial biologic heterogeneity. Liver transplantation (LT) has re-emerged for highly selected patients with unresectable CRLM, but optimal biologic selection criteria remain undefined.

This study integrates genomic and clinical data to develop a biologically grounded framework for surgical and transplant decision-making. The Memorial Sloan Kettering 2017 metastatic colorectal cancer cohort was analyzed using cBioPortal-formatted clinical, genomic, and survival data. The study included patients with liver-only metastatic presentation. Genomic variables comprised KRAS, NRAS, BRAF, TP53, APC, PIK3CA, SMAD4 alterations, tumor mutational burden, microsatellite instability, and copy-number alteration burden.

Survival was assessed using Kaplan-Meier and Cox models. A predefined molecular-risk classification stratified patients into low (RAS/RAF wild-type, SMAD4-intact), intermediate (isolated KRAS mutation), and high risk (NRAS, BRAF, or SMAD4 alterations). Machine-learning models predicted 24-month mortality. Among 503 patients, molecular-risk groups demonstrated distinct survival (5-year OS: 74.5%, 56.6%, and 49.8%; p