Development of an artificial intelligence-derived histologic signature associated with adjuvant gemcitabine treatment outcomes in pancreatic cancer.


Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
18 04 2023
Historique:
received: 31 08 2022
revised: 31 12 2022
accepted: 21 03 2023
medline: 21 4 2023
pubmed: 13 4 2023
entrez: 12 4 2023
Statut: ppublish

Résumé

Pancreatic ductal adenocarcinoma (PDAC) has been left behind in the evolution of personalized medicine. Predictive markers of response to therapy are lacking in PDAC despite various histological and transcriptional classification schemes. We report an artificial intelligence (AI) approach to histologic feature examination that extracts a signature predictive of disease-specific survival (DSS) in patients with PDAC receiving adjuvant gemcitabine. We demonstrate that this AI-generated histologic signature is associated with outcomes following adjuvant gemcitabine, while three previously developed transcriptomic classification systems are not (n = 47). We externally validate this signature in an independent cohort of patients treated with adjuvant gemcitabine (n = 46). Finally, we demonstrate that the signature does not stratify survival outcomes in a third cohort of untreated patients (n = 161), suggesting that the signature is specifically predictive of treatment-related outcomes but is not generally prognostic. This imaging analysis pipeline has promise in the development of actionable markers in other clinical settings where few biomarkers currently exist.

Identifiants

pubmed: 37044094
pii: S2666-3791(23)00123-4
doi: 10.1016/j.xcrm.2023.101013
pmc: PMC10140610
pii:
doi:

Substances chimiques

Gemcitabine 0
Deoxycytidine 0W860991D6
Biomarkers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101013

Informations de copyright

Copyright © 2023 Valar Labs, Inc. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Viswesh Krishna, A.J., D.V., and P.R. are founders of Valar Labs, Inc., and may own stocks. V.N., Vrishab Krishna, E.T., and H.B. are employees of Valar Labs, Inc. E.A.C., D.S., and A.H. are advisors to Valar Labs, Inc.

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Auteurs

Vivek Nimgaonkar (V)

Valar Labs, Inc., Palo Alto, CA, USA.

Viswesh Krishna (V)

Valar Labs, Inc., Palo Alto, CA, USA. Electronic address: viswesh@valarlabs.com.

Vrishab Krishna (V)

Valar Labs, Inc., Palo Alto, CA, USA.

Ekin Tiu (E)

Valar Labs, Inc., Palo Alto, CA, USA.

Anirudh Joshi (A)

Valar Labs, Inc., Palo Alto, CA, USA.

Damir Vrabac (D)

Valar Labs, Inc., Palo Alto, CA, USA.

Hriday Bhambhvani (H)

Valar Labs, Inc., Palo Alto, CA, USA.

Katelyn Smith (K)

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Julia S Johansen (JS)

Departments of Oncology and Medicine, University of Copenhagen, Copenhagen, Denmark.

Shalini Makawita (S)

Baylor College of Medicine, Houston, TX, USA.

Benjamin Musher (B)

Baylor College of Medicine, Houston, TX, USA.

Arnav Mehta (A)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Andrew Hendifar (A)

Cedars Sinai Medical Center, Los Angeles, CA, USA.

Zev Wainberg (Z)

University of California Los Angeles, Los Angeles, CA, USA.

Davendra Sohal (D)

University of Cincinnati Health, Cincinnati, OH, USA.

Christos Fountzilas (C)

Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Aatur Singhi (A)

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Pranav Rajpurkar (P)

Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.

Eric A Collisson (EA)

University of California San Francisco, San Francisco, CA, USA.

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Classifications MeSH