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Record W4392450437 · doi:10.1038/s41525-024-00395-y

Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease

2024· article· en· W4392450437 on OpenAlexafffund
Dhanya Ramachandran, Jonathan P. Tyrer, Stefan Kommoss, Anna DeFazio, Marjorie J. Riggan, David Bowtell, Sián Fereday, Nadia Traficante, Jillian A. Hung, Penelope M. Webb, Peter A. Fasching, Diether Lambrechts, María Jesús García García, Cristina Rodríguez‐Antona, Marc T. Goodman, Francesmary Modugno, Kirsten B. Moysich, Beth Y. Karlan, Jenny Lester, Susanne K. Kjaer, Allan Jensen, Estrid Høgdall, Ellen L. Goode, William A. Cliby, Amanika Kumar, Chen Wang, Julie M. Cunningham, Stacey J. Winham, Álvaro N.A. Monteiro, Joellen M. Schildkraut, Daniel W. Cramer, Kathryn L. Terry, Linda Titus, Line Bjørge, Liv Cecilie Vestrheim Thomsen, Michael Friedländer, Andreas Obermair, Peter Grant, Vanessa L. Beesley, Penelope Blomfield, Alison Brand, Alison Davis, Yee Leung, James Nicklin, Michael C. Quinn, Karen Livingstone, Helen C. O’Neill, Merran Williams, Tanja Pejović, Claus Høgdall, Iain A. McNeish, Taymaa May, David G. Huntsman, Jacobus Pfisterer, Ulrich Canzler, Tjoung‐Won Park‐Simon, W. Schröder, Antje Belau, Lars Hanker, Philipp Harter, Jalid Sehouli, Rainer Kimmig, N de Gregorio, Barbara Schmalfeldt, Klaus Baumann, Felix Hilpert, Alexander Burges, Boris Winterhoff, Peter Schürmann, Lisa‐Marie Speith, Peter Hillemanns, Andrew Berchuck, Sharon E. Johnatty, Susan J. Ramus, Georgia Chenevix‐Trench, Paul D.P. Pharoah, Thilo Dörk, Florian Heitz

Bibliographic record

Venuenpj Genomic Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsPrincess Margaret Cancer CentreUniversity of British ColumbiaUniversity Health Network
FundersMedical Research and Materiel CommandNational Cancer InstituteInstituto de Salud Carlos IIICanadian Institutes of Health ResearchCancer Institute NSWOvarian Cancer Research FundCancer AustraliaNational Institute for Health and Care ResearchNational Health and Medical Research CouncilNorges ForskningsrådMoffitt Cancer CenterMinnesota Ovarian Cancer AllianceWellcome TrustCancer Research UKNational Center for Research ResourcesBC Cancer FoundationFred C. and Katherine B. Andersen FoundationHelse VestOvarian Cancer AustraliaNational Center for Advancing Translational SciencesMedical Research CouncilCancer Research SocietyMayo Foundation for Medical Education and ResearchMinisterio de Economía y CompetitividadUniversity of PittsburghNational Institutes of HealthEuropean CommissionU.S. Department of Defense
KeywordsDebulkingOvarian cancerDiseaseMedicineGenome-wide association studyOncologyGeneCandidate geneGenetic associationInternal medicineBiologyBioinformaticsCancerGeneticsGenotypeSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

Abstract Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT , in HGSOC ( p = 3.9 × 10 −8 ). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.032
Threshold uncertainty score0.796

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.043
GPT teacher head0.340
Teacher spread0.297 · 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 teacher head, 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

Citations5
Published2024
Admission routes2
Has abstractyes

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