Proteogenomic insights suggest druggable pathways in endometrial carcinoma.
CPTAC
CTNNB1
PIK3R1
deep learning
endometrial cancer
metformin
proteogenomics
target assays
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
11 09 2023
11 09 2023
Historique:
received:
14
07
2022
revised:
25
03
2023
accepted:
18
07
2023
pmc-release:
11
09
2024
medline:
14
9
2023
pubmed:
12
8
2023
entrez:
11
8
2023
Statut:
ppublish
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.
Identifiants
pubmed: 37567170
pii: S1535-6108(23)00247-7
doi: 10.1016/j.ccell.2023.07.007
pmc: PMC10631452
mid: NIHMS1921121
pii:
doi:
Substances chimiques
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
beta Catenin
0
Metformin
9100L32L2N
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1586-1605.e15Subventions
Organisme : NCI NIH HHS
ID : U24 CA210954
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214116
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA271076
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210985
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210972
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210955
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210993
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210979
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA271114
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA203690
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM136542
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210967
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210986
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM115313
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA271012
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214114
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214125
Pays : United States
Investigateurs
Andrzej Antczak
(A)
Meenakshi Anurag
(M)
Thomas Bauer
(T)
Chet Birger
(C)
Michael J Birrer
(MJ)
Melissa Borucki
(M)
Shuang Cai
(S)
Anna Calinawan
(A)
Steven A Carr
(SA)
Patricia Castro
(P)
Sandra Cerda
(S)
Daniel W Chan
(DW)
David Chesla
(D)
Marcin P Cieslik
(MP)
Sandra Cottingham
(S)
Rajiv Dhir
(R)
Marcin J Domagalski
(MJ)
Brian J Druker
(BJ)
Elizabeth Duffy
(E)
Nathan J Edwards
(NJ)
Robert Edwards
(R)
Matthew J Ellis
(MJ)
Jennifer Eschbacher
(J)
Mina Fam
(M)
Brenda Fevrier-Sullivan
(B)
Jesse Francis
(J)
John Freymann
(J)
Stacey Gabriel
(S)
Gad Getz
(G)
Michael A Gillette
(MA)
Andrew K Godwin
(AK)
Charles A Goldthwaite
(CA)
Pamela Grady
(P)
Jason Hafron
(J)
Pushpa Hariharan
(P)
Barbara Hindenach
(B)
Katherine A Hoadley
(KA)
Jasmine Huang
(J)
Michael M Ittmann
(MM)
Ashlie Johnson
(A)
Corbin D Jones
(CD)
Karen A Ketchum
(KA)
Justin Kirby
(J)
Toan Le
(T)
Avi Ma'ayan
(A)
Rashna Madan
(R)
Sailaja Mareedu
(S)
Peter B McGarvey
(PB)
Francesmary Modugno
(F)
Rebecca Montgomery
(R)
Kristen Nyce
(K)
Amanda G Paulovich
(AG)
Barbara L Pruetz
(BL)
Liqun Qi
(L)
Shannon Richey
(S)
Eric E Schadt
(EE)
Yvonne Shutack
(Y)
Shilpi Singh
(S)
Michael Smith
(M)
Darlene Tansil
(D)
Ratna R Thangudu
(RR)
Matt Tobin
(M)
Ki Sung Um
(KS)
Negin Vatanian
(N)
Alex Webster
(A)
George D Wilson
(GD)
Jason Wright
(J)
Kakhaber Zaalishvili
(K)
Zhen Zhang
(Z)
Grace Zhao
(G)
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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