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Record W3135532585 · doi:10.1002/ijc.33547

Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients

2021· article· en· W3135532585 on OpenAlexafffund
Angelica Macauda, Chiara Piredda, Alyssa Clay‐Gilmour, Juan Sáinz, Gabriele Buda, Mirosław Markiewicz, Torben Barington, Elad Ziv, Michelle A.T. Hildebrandt, Alem A. Belachew, Judit Várkonyi, Witold Prejzner, Agnieszka Druzd‐Sitek, John J. Spinelli, Niels Frost Andersen, Jonathan N. Hofmann, Marek Dudziński, Joaquín Martínez‐López, Elżbieta Iskierka‐Jazdzewska, Roger L. Milne, Grzegorz Mazur, Graham G. Giles, Lene Hyldahl Ebbesen, Marcin Rymko, Krzysztof Jamroziak, Edyta Subocz, Rui Manuel Reis, Ramón García‐Sánz, Anna Suska, Eva Haastrup, Daria Zawirska, Norbert Grząśko, Annette Juul Vangsted, Charles Dumontet, Marcin Kruszewski, Magdalena Dutka, Nicola J. Camp, Rosalie Waller, Waldemar Tomczak, Matteo Pelosini, Małgorzata Raźny, Herlander Marques, Niels Abildgaard, Marzena Wątek, Artur Jurczyszyn, Elizabeth E. Brown, Sonja I. Berndt, Aleksandra Butrym, Celine M. Vachon, Aaron D. Norman, Susan L. Slager, Federica Gemignani, Federico Canzian, Daniele Campa

Bibliographic record

VenueInternational Journal of Cancer · 2021
Typearticle
Languageen
FieldMedicine
TopicMultiple Myeloma Research and Treatments
Canadian institutionsUniversity of British ColumbiaBC Cancer Agency
FundersNational Cancer InstituteCancer Council VictoriaNational Health and Medical Research CouncilMayo ClinicMedical Research CouncilCanadian Institutes of Health ResearchUniversità di PisaWellcome TrustVicHealthDeutsches KrebsforschungszentrumUniversity of UtahUtah State UniversityHuntsman Cancer InstituteUtah Department of Health
KeywordsMultiple myelomaQuantitative trait locusBiologyTraitGeneGeneticsSurvival analysisOncologyOutcome (game theory)Expression quantitative trait lociInternal medicineMedicineImmunologyGenotypeSingle-nucleotide polymorphism

Abstract

fetched live from OpenAlex

Abstract Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype‐tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10−7 either in EBV‐transformed B‐lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression‐free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4‐rs1992292, TBRG4‐rs2287535 and ENTPD1‐rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta‐analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4‐rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04‐1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.

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)0.001
metaresearch head score (Gemma)0.002
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 score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.002
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 head0.055
GPT teacher head0.375
Teacher spread0.319 · 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

Citations12
Published2021
Admission routes2
Has abstractyes

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