αB-crystallin expression in breast cancer is associated with brain metastasis
Bibliographic record
Abstract
Abstract Background/objectives: The molecular chaperone αB-crystallin is expressed in estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 ‘triple-negative’ breast carcinomas and promotes brain and lung metastasis. We examined αB-crystallin expression in primary breast carcinomas with metastatic data to evaluate its association with prognosis and site-specific metastases. Methods: αB-crystallin gene (CRYAB) expression was examined using publically available global-gene expression data (n=855 breast tumors) with first site of distant metastasis information (‘855Met’). αB-crystallin protein expression was determined by immunohistochemistry using the clinically annotated British Columbia Cancer Agency (BCCA) tissue microarray (n=3,987 breast tumors). Kaplan–Meier and multivariable Cox regression analyses were used to evaluate the prognostic value of αB-crystallin. Multivariable logistic regression analysis was used to evaluate risks of αB-crystallin and other markers for site of metastasis. Results: In the 855Met data set, αB-crystallin gene (CRYAB) expression was an independent predictor of brain as the first distant site of relapse (hazards ratio, HR=1.2, (95% confidence interval, CI 1.0–1.4), P=0.021). In the BCCA series, αB-crystallin protein expression was an independent prognostic marker of poor breast cancer-specific survival (HR=1.3, (95% CI 1.1–1.6), P=0.014). Among patients with metastases, αB-crystallin was the strongest independent predictor of brain metastasis (odds ratio, OR=2.99 (95% CI 1.83–4.89), P<0.0001) and the only independent predictor of brain as the first site of distant metastasis (OR=3.15 (95% CI 1.43–6.95), P=0.005). αB-crystallin was also associated with worse survival (3.0 versus 4.7 months, P=0.007). Conclusions: αB-crystallin is a promising biomarker to identify breast cancer patients at high risk for early relapse in the brain, independent of estrogen receptor and human epidermal growth factor receptor-2 status.
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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 | 0.001 |
| 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".