SFRP1 promoter methylation and its contribution to endometrial tumorigenesis
Bibliographic record
Abstract
B137 Purpose: The secreted frizzled-related protein 1 (SFRP1) encodes a wnt/beta-catenin signalling antagonist and is frequently inactivated by promoter hypermethylation in tumors. We hypothesized that epigenetic inactivation of SFRP1 may be causally involved in the development of endometrial cancer. We undertook a study to examine the contribution of SFRP1 promoter methylation and its association with tumor microsatellite instability (MSI) status among patients with endometrial carcinomas of the endometriod type. Methods: Formalin-fixed, paraffin-embedded tissue sections of endometrial adenocarcinomas and matched normal tissue specimens were obtained from patients (n=56) and DNA was extracted from microdissected specimens enriched for tumor and normal cell populations. MSI status was determined using five National Cancer Institute (NCI) consensus panel markers and the methylation status of SFRP1 promoter was analyzed by methylation-specific PCR (MSPCR) assay of sodium bisulfite treated DNA obtained from these specimens. Beta-catenin expression was assessed in a subset of endometrial tumors by immunohistochemistry. Results: We found that a majority of tumors (87%) show some degree of SFRP1 promoter methylation at the region examined, however 16% of tumors showed exclusive hypermethylation in tumors. There were 30 MSS and 26 MSI endometrial cancer cases. No significant correlation was observed with either tumor MSI status or with strong nuclear beta-catenin expression. Conclusion: Epigenetic inactivation of SFRP1 is a common event in endometrial cancer. It is possible that for a small subset of cases, SFRP1 promoter hypermethylation may play a role in tumorigenesis either through Wnt or an alternative pathway.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".