Publication Date
9-11-2023
Journal
Cancer Cell
DOI
10.1016/j.ccell.2023.07.007
PMID
37567170
PMCID
PMC10631452
PubMedCentral® Posted Date
9-11-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Female, Humans, Proto-Oncogene Proteins c-akt, Prospective Studies, Proteogenomics, Endometrial Neoplasms, beta Catenin, Metformin
Abstract
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.
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Biological Phenomena, Cell Phenomena, and Immunity Commons, Life Sciences Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons, Obstetrics and Gynecology Commons, Oncology Commons
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