Investigating the Roles of YWHAB in Breast Cancer
Bibliographic record
Abstract
Abstract Background: miR-526b and miR-655 have been shown to promote aggressive breast cancer phenotypes. Analysis of cell-free secretions of MCF7-miRNA-high cells identified eight differentially secreted proteins, including 14-3-3 Beta (YWHAB). Here, we investigated the roles of YWHAB in breast cancer and tested its potential as a biomarker. Methods: Breast tumor cell lines MCF7, SKBR3, Hs578T, MCF7-COX2 and stable miRNA-overexpressing MCF7-miR526b, MCF7-miR655, SKBR3-526b cells were used in vitro assays including mRNA, protein expression, and functional assays. In silico data was used to support our findings by identifying potential links between miRNAs and YWHAB and to test diagnostic and prognostic biomarker potential. Biomarker potential was validated using breast tumor biopsy tissue and plasma samples. Results: YWHAB expression is significantly upregulated in miRNA-overexpressing cell lines both at total RNA and secretory RNA levels. These miRNAs have previously been shown to increase cell migration. Following YWHAB-KD cell migration and proliferation decreased, E-Cad expression increased, and Vimentin decreased, evidently showing YWHAB involved in EMT. In silico data showed increased expression of YWHAB mRNA in breast cancer biopsy tissue and blood plasma and increased YWHAB protein in breast tumors. High expression of YWHAB is associated with poor breast cancer patient survival. YWHAB expression was measured in breast tissues and blood plasma and found to be significantly high in all advanced stages and hormonal subtypes of tumors, compared to control tissue. YWHAB showed high sensitivity as a tumour biomarker (AUC of 0.7340, p = 0.0012) and in combination with pri-miR526b showed strong potential as a blood biomarker (AUC of 0.711, p = 0.032). Conclusion: High expression of YWHAB is associated with poor survival. It can be used as a prognostic marker, and therapeutic target in aggressive cancers to mitigate cell migration. In combination with pri-miR526b, YWHAB is a promising blood biomarker for breast cancer detection.
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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 | 0.000 |
| 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 | 0.002 |
| Research integrity | 0.000 | 0.001 |
| 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".