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Record W4408771397 · doi:10.1038/s41588-025-02128-y

The landscape of N6-methyladenosine in localized primary prostate cancer

2025· article· en· W4408771397 on OpenAlexafffund
Xin Xu, Helen He Zhu, Rupert Hugh-White, Julie Livingstone, Stefan E. Eng, Nicole Zeltser, Yujuan Wang, Kinga Pajdzik, Sujun Chen, Kathleen E. Houlahan, Wenqin Luo, Shun Liu, Xi Xu, Minzhi Sheng, Jaron Arbet, Yuxi Song, Miranda Wang, Yong Zeng, Shiyan Wang, Guanghui Zhu, Tingxiao Gao, Wei Chen, Xinpei Ci, Wenjie Xu, Kexin Xu, Michèle Orain, Valérie Picard, Hélène Hovington, Alain Bergeron, Louis Lacombe, Bernard Têtu, Yves Fradet, Mathieu Lupien, Gong‐Hong Wei, Marianne Koritzinsky, Robert G. Bristow, Neil E. Fleshner, Xue Wu, Yang Shao, Chuan He, Alejandro Berlín, Theodorus van der Kwast, Hon S. Leong, Paul C. Boutros, Housheng Hansen He

Bibliographic record

VenueNature Genetics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsUniversité LavalVector InstituteSunnybrook HospitalUniversity Health NetworkUniversity of TorontoPrincess Margaret Cancer Centre
FundersCIHR Skin Research Training CentreNational Cancer InstituteNational Human Genome Research InstituteGovernment of Canada
KeywordsBiologyGermlineProstate cancerDNA methylationGermline mutationTranscriptomeMetastasisSomatic cellGeneticsmicroRNARNACancer researchGeneCancerGene expressionMutation

Abstract

fetched live from OpenAlex

N6-methyladenosine (m6A), the most abundant internal RNA modification in humans, regulates most aspects of RNA processing. Prostate cancer is characterized by widespread transcriptomic dysregulation; therefore, we characterized the m6A landscape of 162 localized prostate tumors with matched DNA, RNA and protein profiling. m6A abundance varied dramatically across tumors, with global patterns emerging via complex germline–somatic cooperative regulation. Individual germline polymorphisms regulated m6A abundance, cooperating with somatic mutation of cancer driver genes and m6A regulators. The resulting complex patterns were associated with prognostic clinical features and established the biomarker potential of global and locus-specific m6A patterns. Tumor hypoxia dysregulates m6A profiles, bridging prior genomic and proteomic observations. Specific m6A sites, such as those in VCAN, drive disease aggression, associating with poor outcomes, tumor growth and metastasis. m6A dysregulation is thus associated with key events in the natural history of prostate cancer: germline risk, microenvironmental dysregulation, somatic mutation and metastasis. Transcriptome-wide m6A RNA methylation profile in 162 primary prostate tumors identifies m6A association with prognostic clinical features and disease aggression.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.008

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 head0.004
GPT teacher head0.269
Teacher spread0.265 · 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

Citations19
Published2025
Admission routes2
Has abstractno

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