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Record W4308057531 · doi:10.1038/s41416-022-02014-y

Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study

2022· article· en· W4308057531 on OpenAlexafffund
Ashley Weir, Eunyoung Kang, Nicola S. Meagher, Gregg Nelson, Prafull Ghatage, Cheng‐Han Lee, Marjorie J. Riggan, Aleksandra Gentry‐Maharaj, Andy Ryan, Naveena Singh, Martin Widschwendter, Jennifer Alsop, Michael S. Anglesio, Matthias W. Beckmann, Jessica Berger, Christiani Bisinotto, Jessica Boros, Alison H. Brand, James D. Brenton, Angela Brooks‐Wilson, Michael E. Carney, Julie M. Cunningham, Kara L. Cushing‐Haugen, Cezary Cybulski, Esther Elishaev, Ramona Erber, Sián Fereday, Anna Fischer, Luis Paz‐Ares, Javier Machín Gayarre, Blake C. Gilks, Marcel Grube, Paul R. Harnett, Holly R. Harris, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y. Hernandez, Sabine Heublein, Yajue Huang, Tomasz Huzarski, Anna Jakubowska, Mercedes Jimenez‐Liñan, Catherine J. Kennedy, F. Kommoss, Jennifer M. Koziak, Bernhard Kraemer, Nhu D. Le, Jaime Lesnock, Jenny Lester, Jan Lubiński, Janusz Menkiszak, Britta Ney, Alexander Olawaiye, Sandra Oršulić, Ana Osório, Luis A. Díaz‐Robles, Matthias Ruebner, Mitul Shah, Raghwa Sharma, Yurii B. Shvetsov, Helen Steed, Aline Talhouk, Sarah E. Taylor, Nadia Traficante, Robert A. Vierkant, Chen Wang, Lynne R. Wilkens, Stacey J. Winham, Javier Benı́tez, Andrew Berchuck, David D.L. Bowtell, Francisco José Cândido dos Reis, Linda S. Cook, Anna DeFazio, Jennifer A. Doherty, Peter A. Fasching, María J. García, Ellen L. Goode, Marc T. Goodman, Jacek Gronwald, David G. Huntsman, Beth Y. Karlan, Stefan Kommoss, Francesmary Modugno, Joellen M. Schildkraut, Hans‐Peter Sinn, Annette Staebler, Linda E. Kelemen, Caroline E. Ford, Usha Menon, Paul D.P. Pharoah, Martin Köbel, Susan J. Ramus

Bibliographic record

VenueBritish Journal of Cancer · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicFOXO transcription factor regulation
Canadian institutionsAlberta Health ServicesCanada's Michael Smith Genome Sciences CentreVancouver General HospitalUniversity of British ColumbiaFoothills Medical CentreUniversity of AlbertaUniversity of Calgary
FundersMedical Research and Materiel CommandNational Center for Advancing Translational SciencesEuropean Regional Development FundInstituto de Salud Carlos IIICancer Council TasmaniaNational Health and Medical Research CouncilHorizon 2020 Framework ProgrammeNational Institutes of HealthTranslational Cancer Research NetworkUniversity College LondonCancer Institute NSWNational Cancer InstitutePeter MacCallum FoundationNSW Ministry of HealthAmerican Cancer SocietyCancer Council South AustraliaPomorski Uniwersytet Medyczny W SzczecinieOvarian Cancer Research FundMinisterio de Economía y CompetitividadCancer Council VictoriaUniversity of PittsburghUniversity of New South WalesCancer Council NSWUniversität HeidelbergCanadian Institutes of Health ResearchMedical Research CouncilDepartment of Health and Social CareNational Institute for Health and Care ResearchMichael Smith Health Research BCCanada Research ChairsNIHR Cambridge Biomedical Research CentreUniversity of CambridgeFred C. and Katherine B. Andersen FoundationCancer AustraliaOvarian Cancer ActionCalgary Laboratory ServicesMayo Foundation for Medical Education and ResearchDeutsche ForschungsgemeinschaftVGH and UBC Hospital FoundationU.S. Department of DefenseCancer Research UKMinnesota Ovarian Cancer AllianceNational Center for Research ResourcesBC Cancer FoundationOak FoundationOvarian Cancer AustraliaConselho Nacional de Desenvolvimento Científico e TecnológicoCancer Research SocietyEuropean Commission
KeywordsImmunohistochemistrySerous carcinomaSerous fluidTissue microarrayOvarian carcinomaOvarian cancerOncologyUnivariate analysisSurvival analysisMedicinePathologyBiologyMultivariate analysisInternal medicineCancer

Abstract

fetched live from OpenAlex

BACKGROUND: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC. METHODS: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis. RESULTS: Consistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p < 0.0001). GMNN protein expression was not significantly associated with overall HSGC patient survival. However, HGSCs with >35% GMNN expression showed a trend for better outcomes, though this was not significant. CONCLUSION: We provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

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)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.709
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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 head0.010
GPT teacher head0.247
Teacher spread0.237 · 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

Citations7
Published2022
Admission routes2
Has abstractyes

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