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Record W4283157743 · doi:10.1101/2022.06.13.495375

Receptor for Hyaluronan-Mediated Motility (RHAMM) defines an invasive niche associated with tumor progression and predicts poor outcomes in breast cancer patients

2022· preprint· en· W4283157743 on OpenAlexafffund
Sarah E Tarullo, Yuyu He, Claire Daughters, Todd P. Knutson, Christine Henzler, Matt A. Price, Ryan Shanley, Patrice M. Witschen, Cornelia Tölg, Rachael E. Kaspar, Caroline Hallstrom, Lyubov Gittsovich, Megan L. Sulciner, Xihong Zhang, Colleen Forester, Oleg Shats, Michelle Desler, Kenneth H. Cowan, Douglas Yee, Kathryn L. Schwertfeger, Eva A. Turley, James B. McCarthy, Andrew C. Nelson

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProteoglycans and glycosaminoglycans research
Canadian institutionsLondon Health Sciences CentreWestern University
FundersNational Center for Advancing Translational SciencesMasonic Cancer Center, University of MinnesotaNational Institutes of HealthBreast Cancer Society of CanadaUniversity of MinnesotaAmerican Cancer Society
KeywordsTumor microenvironmentTumor progressionMotilityBiologyCancer researchBreast cancerMetastasisCancerTranscriptomeImmunologyGene expressionCell biologyGeneGeneticsTumor cells

Abstract

fetched live from OpenAlex

ABSTRACT Breast cancer invasion and metastasis result from a complex interplay between tumor cells and the tumor microenvironment (TME). Key oncogenic changes in the TME include aberrant metabolism and subsequent signaling of hyaluronan (HA). Hyaluronan Mediated Motility Receptor (RHAMM, HMMR ) is a HA receptor that enables tumor cells to sense and respond to the TME during breast cancer progression. Focused gene expression analysis of an internal breast cancer patient cohort demonstrates increased RHAMM expression correlates with aggressive clinicopathological features. We also develop a 27-gene RHAMM-dependent signature (RDS) by intersecting differentially expressed genes in lymph node positive cases with the transcriptome of a RHAMM-dependent model of cell transformation, which we validate in an independent cohort. We demonstrate RDS predicts for poor survival and associates with invasive pathways. Further analyses using CRISPR/Cas9 generated RHAMM -/- breast cancer cells provide direct evidence that RHAMM promotes invasion in vitro and in vivo . Additional immunohistochemistry studies highlight heterogeneous RHAMM expression, and spatial transcriptomics confirms the RDS emanates from RHAMM-high invasive niches. We conclude RHAMM upregulation leads to the formation of ‘invasive niches’, which are enriched in RDS-related pathways that drive invasion and could be targeted to limit invasive progression and improve patient outcomes.

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)0.000
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 score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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)0.0020.000

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 head0.012
GPT teacher head0.254
Teacher spread0.241 · 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

Citations1
Published2022
Admission routes2
Has abstractyes

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