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Record W4410383109 · doi:10.1038/s41598-025-00866-x

Tumor budding and poorly differentiated clusters as a biological continuum in colorectal cancer invasion and prognosis

2025· article· en· W4410383109 on OpenAlexaff
Tariq Sami Haddad, John‐Melle Bokhorst, Luuk van den Dobbelsteen, Sonay Kuş Öztürk, Elias Baumann, Shannon van Vliet, Kiek Verrijp, Nigel B. Jamieson, Colin S. Wood, Martin D. Berger, Richard Kirsch, Marco Aben, Natasja Rutgers, Hideki Ueno, Francesco Ciompi, Femke Simmer, Jeroen van der Laak, Alessandro Lugli, Inti Zlobec, Irıs D. Nagtegaal

Bibliographic record

VenueScientific Reports · 2025
Typearticle
Languageen
FieldMedicine
TopicFerroptosis and cancer prognosis
Canadian institutionsMount Sinai Hospital
FundersKWF Kankerbestrijding
KeywordsTumor buddingColorectal cancerBuddingBiologyCancer researchComputational biologyCancerEvolutionary biologyGeneticsMetastasis

Abstract

fetched live from OpenAlex

Tumor budding (TB) and poorly differentiated clusters (PDCs) are features of infiltrative growth patterns and powerful independent prognostic factors in colorectal cancer (CRC), yet the underlying biological mechanisms behind their role in CRC invasion is less understood. The aim of this study was to investigate the molecular background and prognostic role of tumor cluster size at the invasive margin (IM) of CRC, and determine whether a biological continuum between TB and PDCs exists. Using a combination of spatial transcriptomic and immunohistochemical (IHC) techniques, we demonstrated a biological continuum from larger to smaller tumor clusters, with TB possessing greater invasive potential than PDCs. We deployed artificial intelligence on a cohort of 1134 Stage I-III CRC resections to automatically detect nearly 400,000 isolated tumor cells/clusters of any particular size across the IM. We determined that 2-celled clusters were the most abundant feature at the IM, and the simultaneous assessment of TB and PDCs yielded a prognostic performance stronger than either independently. Our study provides a deeper understanding of the mechanisms behind CRC invasion while improving risk stratification for Stage I-III CRC.

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)0.001
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 score0.002
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
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 head0.019
GPT teacher head0.285
Teacher spread0.266 · 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

Citations10
Published2025
Admission routes1
Has abstractyes

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