MétaCan
Menu
Back to cohort
Record W2801812177 · doi:10.1073/pnas.1720588115

Mutations in the pancreatic secretory enzymes <i>CPA1</i> and <i>CPB1</i> are associated with pancreatic cancer

2018· article· en· W2801812177 on OpenAlexaff
Jun Yu, Tatsuo Hata, Masaya Suenaga, Koji Shindo, Toshiya Abe, Anne Macgregor-Das, Michael Borges, Christopher L. Wolfgang, Matthew J. Weiss, Jin He, Marcia Irene Canto, Gloria M. Petersen, Steven Gallinger, Sapna Syngal, Randall E. Brand, Anil K. Rustgi, Sara H. Olson, Elena M. Stoffel, Michele L. Coté, George Zogopoulos, James B. Potash, Fernando S. Goes, W. Richard McCombie, Peter P. Zandi, Mehdi Pirooznia, Melissa Kramer, Jennifer Parla, James R. Eshleman, Nicholas J. Roberts, Ralph H. Hruban, Alison P. Klein, Michael Goggins

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2018
Typearticle
Languageen
FieldMedicine
TopicPancreatic and Hepatic Oncology Research
Canadian institutionsMcGill University Health CentreLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersNational Cancer Institute
KeywordsPancreatic cancerEnzymePancreatic enzymesBiologyInternal medicineEndocrinologyBiochemistryGeneticsMedicineCancer

Abstract

fetched live from OpenAlex

Significance Much of the inherited susceptibility to pancreatic cancer remains unexplained. Germline variants that cause protein misfolding and impaired secretion of pancreatic enzymes such as CPA1 (encoding carboxypeptidase A1) can cause pancreatic acinar cell endoplasmic reticulum (ER) stress. We investigated the hypothesis that pancreatic cancer could arise from germline variants in genes encoding pancreatic secretory enzymes that induce pancreatic acinar cell stress. We find ∼1% of 1,579 patients with pancreatic cancer vs. 1 of 2,012 controls have germline variants in the genes encoding CPA1 and CPB1 (carboxypeptidase B1) that impair secretion of its protein product and induce ER stress. These findings implicate pancreatic acinar cell stress as a mechanism of pancreatic cancer susceptibility.

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 score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.055
GPT teacher head0.356
Teacher spread0.301 · 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

Citations94
Published2018
Admission routes1
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicPancreatic and Hepatic Oncology ResearchFrench-language works237,207