biostudies-literatureUnknown24(1)Hyeon DYWe 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 characMolecular cancer77https://www.ebi.ac.uk/biostudies/studies/S-EPMC11908047biostudies-literatureProteogenomic characterization of molecular and cellular targets for treatment-resistant subtypes in locally advanced cervical cancers.PMC11908047Kim SSKim HKu JLHong EKPark KSChoi WYoo CWKim JYKang CMadar IHBaek HJKang JShin DHKim SJShin YShin HJBae JBack SJeong JJung ELee SJJung KNam DKim JKBae YKHyeon DYLim MCKim DKKim SHwang DPark GWLee SWCho SYfalseProteogenomic characterization of molecular and cellular targets for treatment-resistant subtypes in locally advanced cervical cancers.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 charac2025-01-01T00:00:00Z2025 Mar2026-06-02T07:17:11.478Z2025-04-05T12:39:00.238ZS-EPMC119080474008774510.1186/s12943-025-02256-3