Proteogenomic insights suggest druggable pathways in endometrial carcinoma.
Cancer Cell
; 41(9): 1586-1605.e15, 2023 09 11.
Article
em En
| MEDLINE
| ID: mdl-37567170
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 ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
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Proteogenômica
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Metformina
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article