Proteogenomic insights suggest druggable pathways in endometrial carcinoma

Clinical Proteomic Tumor Analysis Consortium

Résultat de rechercheexamen par les pairs

17 Citations (Scopus)

Résumé

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

Langue d'origineEnglish
Pages (de-à)1586-1605.e15
JournalCancer Cell
Volume41
Numéro de publication9
DOI
Statut de publicationPublished - sept. 11 2023

Financement

Bailleurs de fondsNuméro du bailleur de fonds
Clinical Proteomic Tumor Analysis Consortium
Janice McNair Foundation
McNair Medical Institute
National Scientific User Facility
National Institutes of HealthS21-167, U24CA210955, U24CA210954, U24CA210979, U24CA210967, U24CA210972, U24CA210986, U24CA210985, U24CA271012, U24CA210993, U24CA271076, U01CA214116, U01CA214114, U01CA214125, 21X164Q, U24CA271114
U.S. Department of DefenseDOD BC220523
U.S. Department of EnergyDE-AC05-76RL01830
National Cancer InstituteT32CA203690, RR160027
Battelle
Cancer Prevention and Research Institute of Texas
Pacific Northwest National Laboratory

    ASJC Scopus Subject Areas

    • Oncology
    • Cancer Research

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