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Record W4410911666 · doi:10.1101/2025.05.29.25328569

Plasma cell-free DNA methylome as early detection and prognostic marker for pancreatic cancer

2025· preprint· en· W4410911666 on OpenAlexaff
Sanjeev Budhathoki, Yonathan Brhane, Gordon Fehringer, Shu Shen, Dianne Chadwick, Philip C. Zuzarte, Ayelet Borgida, Daniel D. De Carvalho, Steven Gallinger, Rayjean J. Hung

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicPancreatic and Hepatic Oncology Research
Canadian institutionsPublic Health OntarioOntario Institute for Cancer ResearchToronto General HospitalUniversity of TorontoUniversity Health NetworkPrincess Margaret Cancer CentreSinai Health SystemOccupational Cancer Research CentreLunenfeld-Tanenbaum Research Institute
Fundersnot available
KeywordsDNA methylationCell-free fetal DNACancerDNAPancreatic cancerCancer researchCellBiologyMedicineInternal medicineGeneGeneticsGene expression

Abstract

fetched live from OpenAlex

Abstract Pancreatic cancer is highly fatal, with limited early detection options. Here, we conducted a study to evaluate the potential use of circulating cell-free DNA methylation for pancreatic cancer early detection and prognosis. Using a highly sensitive enrichment-based sequencing technology, we profiled genome-wide circulating cell-free methylome of 199 pancreatic cancer patients and 205 healthy individuals. We identified a panel of differentially methylated regions in cell-free DNA that distinguished pancreatic cancer cases from controls with high accuracy (test set AUC=0.93, 95%CI=0.88-0.98), notably robust accuracy for early-stage pancreatic cancer (AUC=0.92, 95%CI=0.86-0.98). We also identified a panel of cfDNA methylated regions that effectively stratified patients into longer or shorter survival groups, which was independently validated in The Cancer Genome Atlas cohort (HR=1.37, 95%CI=1.00-1.88, p=0.049). These results provide support for the potential utility of cell-free DNA methylation markers for both early detection and prognosis in pancreatic cancer, presenting a promising tool for enhancing patient management.

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 score0.005

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)0.0020.000

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 head0.031
GPT teacher head0.341
Teacher spread0.310 · 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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Same venuemedRxiv→Same topicPancreatic and Hepatic Oncology Research→French-language works237,207→