Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer.
chemorefractory
high-grade serous ovarian cancer
machine learning
mass spectrometry
multiple reaction monitoring
platinum
precision oncology
predictive biomarker
prognostic biomarker
proteogenomic
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
03 08 2023
03 08 2023
Historique:
received:
30
09
2022
revised:
23
03
2023
accepted:
05
07
2023
medline:
7
8
2023
pubmed:
5
8
2023
entrez:
4
8
2023
Statut:
ppublish
Résumé
To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.
Identifiants
pubmed: 37541199
pii: S0092-8674(23)00737-7
doi: 10.1016/j.cell.2023.07.004
pmc: PMC10414761
mid: NIHMS1918576
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3476-3498.e35Subventions
Organisme : NCI NIH HHS
ID : U24 CA210954
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA271037
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015704
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210967
Pays : United States
Organisme : NIH HHS
ID : S10 OD028685
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211499
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210972
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA015083
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210993
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA240139
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214114
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA271114
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA136393
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.J.B. has participated in advisory boards for the following companies: Clovis, Astra Zeneca, and GSK-Tesaro. A.N.H. is the Associate Editor of Clinical Chemistry and has a financial interest in the company Seattle Genetics. A.G.P. is the founder of Precision Assays, LLC. A.B.B. is employed by Synapse. S.Y. is an employee and shareholder of Sema4. B.J.W. has stock interests in Verastem and Exact Sciences.
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