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Record W4392750609 · doi:10.1038/s41698-024-00519-8

Proteogenomic analysis of enriched HGSOC tumor epithelium identifies prognostic signatures and therapeutic vulnerabilities

2024· article· en· W4392750609 on OpenAlexaff
Nicholas W. Bateman, Tamara Abulez, Anthony R. Soltis, Andrew McPherson, Seongmin Choi, Dale W. Garsed, Ahwan Pandey, Chunqiao Tian, Brian L. Hood, Kelly A. Conrads, Pang-ning Teng, Julie Oliver, Glenn Gist, Dave Mitchell, Tracy J. Litzi, Christopher M. Tarney, Barbara A. Crothers, Paulette Mhawech‐Fauceglia, Clifton L. Dalgard, Matthew D. Wilkerson, Mariaelena Pierobon, Emanuel F. Petricoin, Chunhua Yan, Daoud Meerzaman, Clara Bodelón, Nicolas Wentzensen, Jerry Lee, Sasha C. Makohon‐Moore, Waleed Barakat, Xijun Zhang, Allison L. Hunt, Wei Ao, Stacey L. Lytle-Gabbin, Yovanni Casablanca, Chad A. Hamilton, Miranda Newell, J. Mitchell Wells, Gauthaman Sukumar, Dagmar Bačíková, John Freyman, David E. Cohn, Andrew Berchuck, Laura J. Havrilesky, Linda Duska, Adekunle Odunsi, Anil K. Sood, James D. Brenton, Evis Sala, Christina M. Annunziata, Oliver Dorigo, Brad H. Nelson, Dawn R. Cochrane, Kathleen Moore, Elisa Baldelli, Qing-rong Chen, Ying Hu, Sián Fereday, Nadia Traficante, Anna DeFazio, Ellen L. Goode, David G. Huntsman, Sohrab P. Shah, Craig D. Shriver, Neil T. Phippen, Kathleen M. Darcy, David D.L. Bowtell, Thomas P. Conrads, G. Larry Maxwell

Bibliographic record

Venuenpj Precision Oncology · 2024
Typearticle
Languageen
FieldMedicine
TopicFerroptosis and cancer prognosis
Canadian institutionsUniversity of British Columbia
FundersNational Cancer InstituteNational Health and Medical Research CouncilMedical Research CouncilInova Health SystemUniformed Services University of the Health SciencesOhio State UniversityHenry M. Jackson FoundationU.S. Department of Defense
KeywordsLaser capture microdissectionCancer researchMedicineWee1CancerPathologyInternal medicineBiologyCell cycleGeneGene expressionCyclin-dependent kinase 1

Abstract

fetched live from OpenAlex

We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched tumor cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning a broad spectrum of purity. We identified patients with longer progression-free survival had increased immune-related signatures and validated proteins correlating with tumor-infiltrating lymphocytes in 65 tumors from an independent cohort of HGSOC patients, as well as with overall survival in an additional 126 HGSOC patient cohort. We identified that homologous recombination deficient (HRD) tumors are enriched in pathways associated with metabolism and oxidative phosphorylation that we validated in independent patient cohorts. We further identified that polycomb complex protein BMI-1 is elevated in HR proficient (HRP) tumors, that elevated BMI-1 correlates with poor overall survival in HRP but not HRD HGSOC patients, and that HRP HGSOC cells are uniquely sensitive to BMI-1 inhibition.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.331
Teacher spread0.308 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2024
Admission routes1
Has abstractyes

Explore more

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