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Record W4220818710 · doi:10.1038/s41467-022-29040-x

Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

2022· article· en· W4220818710 on OpenAlexaff
Nanda Horeweg, Hagma H. Workel, Dominik Loiero, David N. Church, Lisa Vermij, Alicia León‐Castillo, Ricki T. Krog, Stephanie M. de Boer, Remi A. Nout, Melanie Powell, Linda Mileshkin, Helen Mackay, Alexandra Léary, Naveena Singh, Ina M. Jürgenliemk‐Schulz, Vincent T.H.B.M. Smit, Carien L. Creutzberg, Viktor H. Koelzer, Hans W. Nijman, Tjalling Bosse, Marco de Bruyn

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicEndometrial and Cervical Cancer Treatments
Canadian institutionsSunnybrook Health Science Centre
FundersPromedica StiftungLeids Universitair Medisch CentrumWellcome TrustAcademy of Medical SciencesKWF KankerbestrijdingNational Institute for Health and Care ResearchCancer Research UKWellcome
KeywordsEndometrial cancerLymphatic systemCancerMedicineCancer researchBiologyOncologyInternal medicinePathology

Abstract

fetched live from OpenAlex

B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naïve B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis shows association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence show L1CAM expression in mature TLS, independent of L1CAM expression in the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank are evaluated, TLS are found in 19%. L1CAM expressing TLS are most common in mismatch-repair deficient (29/127, 23%) and polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression analysis shows strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker.

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)0.000
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 score0.145
Threshold uncertainty score0.423

Codex and Gemma teacher scores by category

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 integrity0.0000.001
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 head0.034
GPT teacher head0.375
Teacher spread0.341 · 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

Citations144
Published2022
Admission routes1
Has abstractyes

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