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Record W4304758122 · doi:10.1158/1078-0432.ccr-22-1206

Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

2022· article· en· W4304758122 on OpenAlexafffund
Nicola S. Meagher, Kylie L. Gorringe, Matthew J. Wakefield, Adelyn Bolithon, Chi Nam Ignatius Pang, Derek S. Chiu, Michael S. Anglesio, Kylie‐Ann Mallitt, Jennifer A. Doherty, Holly R. Harris, Joellen M. Schildkraut, Andrew Berchuck, Kara L. Cushing‐Haugen, Ksenia Chezar, Angela Chou, Adeline Tan, Jennifer Alsop, Ellen Barlow, Matthias W. Beckmann, Jessica Boros, David D.L. Bowtell, Alison H. Brand, James D. Brenton, Ian Campbell, Dane Cheasley, Joshua G. Cohen, Cezary Cybulski, Esther Elishaev, Ramona Erber, Rhonda Farrell, Anna Fischer, Zhuxuan Fu, C. Blake Gilks, Anthony J. Gill, Charlie Gourley, Marcel Grube, Paul R. Harnett, Arndt Hartmann, Anusha Hettiaratchi, Claus Høgdall, Tomasz Huzarski, Anna Jakubowska, Mercedes Jimenez‐Liñan, Catherine J. Kennedy, Byoung‐Gie Kim, Jae‐Weon Kim, Jae‐Hoon Kim, Kayla Klett, Jennifer M. Koziak, Tiffany Lai, Angela Laslavic, Jenny Lester, Yee Leung, Na Li, Winston Liauw, Belle W.X. Lim, Anna Linder, Jan Lubiński, Sakshi Mahale, Constantina Mateoiu, Simone McInerny, Janusz Menkiszak, Parham Minoo, Suzana Mittelstadt, David L. Morris, Sandra Oršulić, Sang‐Yoon Park, Celeste Leigh Pearce, John V. Pearson, Malcolm C. Pike, Carmel M. Quinn, Ganendra Raj Mohan, Jianyu Rao, Marjorie J. Riggan, Matthias Ruebner, Stuart Salfinger, Clare L. Scott, Mitul Shah, Helen Steed, Colin J.R. Stewart, Deepak Subramanian, Soseul Sung, Katrina Tang, Paul Timpson, Robyn L. Ward, Rebekka Wiedenhoefer, Heather Thorne, Paul A. Cohen, Philip Crowe, Peter A. Fasching, Jacek Gronwald, Nicholas J. Hawkins, Estrid Høgdall, David G. Huntsman, Paul A. James, Beth Y. Karlan, Linda E. Kelemen, Stefan Kommoss, Gottfried E. Konecny, Francesmary Modugno, Sue K. Park, Annette Staebler, Karin Sundfeldt, Anna H. Wu, Aline Talhouk, Paul D.P. Pharoah, Lyndal Anderson, Anna DeFazio, Martin Köbel, Michael Friedländer, Susan J. Ramus

Bibliographic record

VenueClinical Cancer Research · 2022
Typearticle
Languageen
FieldMedicine
TopicOvarian cancer diagnosis and treatment
Canadian institutionsUniversity of Alberta HospitalUniversity of AlbertaBC Cancer AgencyFoothills Medical CentreAlberta Health ServicesUniversity of British ColumbiaCanadian Centre for Applied Research in Cancer ControlVancouver General Hospital
FundersNational Cancer InstituteCancer Council TasmaniaCancer Council South AustraliaBC Cancer FoundationNational Center for Advancing Translational SciencesMedical Research CouncilPeter MacCallum FoundationMedical Research and Materiel CommandNSW Ministry of HealthCancer Council VictoriaUniversity of New South WalesCanadian Institutes of Health ResearchCancer Institute NSWOvarian Cancer Research FundCancer AustraliaUniversity of CambridgeUniversity of PittsburghCalgary Laboratory ServicesOvarian Cancer ActionMichael Smith Health Research BCFaculty of Medicine and Health, University of SydneyTranslational Cancer Research NetworkKorea Health Industry Development InstituteNational Institute for Health and Care ResearchCancer Council NSWOvarian Cancer AustraliaNational Institutes of HealthU.S. Department of DefenseNational Health and Medical Research CouncilCancer Research UKNational Science Foundation
KeywordsGene expression profilingOvarian cancerOncologyGene expressionCancer researchBiologyPathologyMedicineInternal medicineGeneCancerGenetics

Abstract

fetched live from OpenAlex

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

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)0.001
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.097
GPT teacher head0.427
Teacher spread0.331 · 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".

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Citations21
Published2022
Admission routes2
Has abstractyes

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