Promoter polymorphisms of the SWI/SNF chromatin remodeling complex molecule, BRM, and esophageal adenocarcinoma outcome.
Bibliographic record
Abstract
4077 Background: Better understanding of the biology of esophageal cancer may help improve its treatment. The SWI/SNF chromatin remodeling complex is an important regulator of gene expression that has been linked to cancer development and outcome. Expression of Brahma (BRM), a critical catalytic subunit of SWI/SNF, is lost in a variety of solid tumors. Two novel BRM promoter polymorphisms (BRM -741 and BRM -1321) have been correlated with BRM loss and elevated cancer risk in upper aerodigestive cancers (Wang et al, Carcinogenesis, 2012) and more recently in lung cancer outcome (Cuffe et al, ESMO, 2012) by our research teams. Objectives: We evaluated BRM polymorphisms and their role in the survival of esophageal cancer patients. Methods: 223 histologically-confirmed esophageal adenocarcinoma patients of all stages were evaluated. The two BRM polymorphisms utilized Taqman genotyping. Cox proportional hazards models adjusted for clinical prognostic variables and determined the association of polymorphisms with overall survival (OS) and progression free survival (PFS). Adjusted hazard ratio (aHR) and 95% confidence intervals (CI) were calculated. Results: Among our patients, 85% were male; the mean age was 63 years. 37% had stage IV advanced tumors. The median PFS was 1.03 years, while median OS was 1.82 years. After adjustment for known prognostic clinical variables, carrying homozygous variants of both BRM polymorphisms (double homozygotes) was associated with a worse outcome: aHR 1.84 (1.06-2.34, p=0.03) for OS and aHR 1.93 (1.10-2.48, p=0.02) for PFS. The direction and magnitude of associations were similar in subsets of patients by age, gender, smoking status, use of platinum agents, and disease stage. Non-significant trends in the same direction but of aHR magnitudes 1.34-1.54 were seen in the patients who carried one homozygous variant or who were double heterozygotes. Conclusions: We report the initial association of BRM polymorphisms with survival in esophageal cancer. We plan to explore additional relationships and validate these findings in other datasets.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 teacher head, 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".