Proteogenomic characterization of molecular and cellular targets for treatment-resistant subtypes in locally advanced cervical cancers.

ABSTRACT: We report proteogenomic analysis of locally advanced cervical cancer (LACC). Exome-seq data revealed predominant alterations of keratinization-TP53 regulation and O-glycosylation-TP53 regulation axes in squamous and adeno-LACC, respectively, compared to in early-stage cervical cancer. Integrated clustering of mRNA, protein, and phosphorylation data identified six subtypes (Sub1-6) of LACC among which Sub3, 5, and 6 showed the treatment-resistant nature with poor local recurrence-free survival. Elevated immune and extracellular matrix (ECM) activation mediated by activated stroma (PDGFD and CXCL1^high fibroblasts) characterized the immune-hot Sub3 enriched with MUC5AC^high epithelial cells (ECs). Increased epithelial-mesenchymal-transition (EMT) and ECM remodeling charac

SUBMITTER: Hyeon DY 

PROVIDER: S-EPMC11908047 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature