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Record W4413344407 · doi:10.1101/2025.08.13.670169

A prognostic signature for lung adenocarcinoma in people who have never smoked

2025· preprint· en· W4413344407 on OpenAlexaff
Wei Zhao, Tongwu Zhang, Xing Hua, Phuc H. Hoang, Mona Miraftab, Monjoy Saha, John McElderry, Jian Sang, Olivia W. Lee, Caleb Hartman, Azhar Khandekar, Sunandini Sharma, Frank J. Colón-Matos, Samuel Anyaso‐Samuel, Difei Wang, Kristine Jones, Amy Hutchinson, Belynda Hicks, Jennifer Rosenbaum, Xiaoming Zhong, Yang Yang, Angela Cecilia Pesatori, Dario Consonni, David C. Christiani, Kin Chung Leung, Maria P. Wong, Marta Mańczuk, Jolanta Lissowska, Beata Świątkowska, Anush Mukeria, Oxana Shangina, David Zaridze, Ivana Holcátová, Dana Mateș, Saša Milosavljević, Simona Ognjanovic, Milan Savić, Milica Kontić, Valérie Gaborieau, Paul Brennan, Óscar Arrieta, Yohan Bossé, Eric S. Edell, Matthew B. Schabath, Paul L. Hofman, Luís Más, Sai Yendamuri, Chih-Yi Chen, I–Shou Chang, Chao A. Hsiung, Geoffrey Liu, Bonnie E. Gould Rothberg, Karun Mutreja, Scott M. Lawrence, Nathaniel Rothman, Ludmil B. Alexandrov, Charles Leduc, Marina K. Baine, Philippe Joubert, Lynette M. Sholl, William D. Travis, Robert Homer, Qing Lan, Stephen J Chanock, Lixing Yang, Soo-Ryum Yang, Jianxin Shi, Maria Teresa Landi

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldMedicine
TopicFerroptosis and cancer prognosis
Canadian institutionsCentre Hospitalier de l’Université de MontréalPrincess Margaret Cancer CentreUniversité LavalInstitut universitaire de cardiologie et de pneumologie de Québec
FundersNational Institutes of HealthWorld Health OrganizationU.S. Department of Health and Human Services
KeywordsSignature (topology)AdenocarcinomaLungMedicineInternal medicineOncologyPathologyCancerMathematics

Abstract

fetched live from OpenAlex

Abstract Knowledge of tumor cell dynamics can inform prognosis and treatment yet is largely lacking for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA-seq data from 684 NS-LUAD and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histological data further characterized the subtypes. ‘Steady’ , marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver genes’ alterations, is linked to prolonged survival and low immune evasion. ‘Proliferative ’ shows high proliferation markers, TP53 mutations, and gene fusions. ‘Chaotic’ , with high epithelial-to-mesenchymal transition markers, has the worst prognosis even within stage I tumors. Lacking known molecular or histological characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the overall classification and strongly predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving NS-LUAD prognostication in clinical settings. Significance The transcriptome of 684 lung adenocarcinomas in people who have never smoked (NS-LUAD) identifies three subtypes with different cellular dynamics, and genomic and morphologic features. A 60-gene signature accurately stratifies subjects for mortality risk, even in stage I, offering a clinically applicable tool for treatment decision making in NS-LUAD 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)0.000
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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.014
GPT teacher head0.249
Teacher spread0.235 · 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

Citations0
Published2025
Admission routes1
Has abstractyes

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