Proteogenomic Characterization Reveals Metabolic Vulnerabilities and Aberrant Phosphorylation in Colorectal Metastasis to Liver.

ABSTRACT: Colorectal liver metastasis (CRLM) is one of the leading death causes among colorectal cancer (CRC) patients, yet its underlying molecular events remain poorly understood, particularly at the proteomic and phosphoproteomic levels. A proteogenomic analysis combining genomics, transcriptomics, proteomics, and phosphoproteomics is performed on 102 samples from 34 treatment-naïve CRLM patients, including primary CRC, adjacent normal colorectal, and matched liver metastasis tissues. CRC cell lines, organoids, mouse models, and an independent patient cohort are used to validate the findings. Proteomics and phosphoproteomics show profoundly dysregulated pathways in liver metastasis tissues, notably disruptions in carbon metabolism. Functional validation using CRC organoids and mouse models demons

SUBMITTER: Zhao W 

PROVIDER: S-EPMC12822478 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature