αB-crystallin expression in breast cancer is associated with brain metastasis
Why this work is in the frame
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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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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 | 0.000 | 0.000 |
| 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) | 0.001 | 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 it