EMT Features in Claudin-Low versus Claudin-Non-Suppressed Breast Cancers and the Role of Epigenetic Modifications
Bibliographic record
Abstract
BACKGROUND: Breast cancers are heterogeneous and are classified according to the expression of ER, PR and HER2 receptors to distinct groups with prognostic and therapeutic implications. Within the triple-negative group, with no expression of these three receptors, molecular heterogeneity exists but is currently not exploited in the clinic. The claudin-low phenotype is present in a subset of triple-negative breast cancers and constitutes together with basal-like cancers the most extensive groups within triple-negative breast cancers. Suppression of epithelial cell adhesion molecules in claudin-low cancers is also a hallmark of Epithelial Mesenchymal Transition (EMT). METHODS: The groups of claudin-low and claudin-non-suppressed breast cancers from the extensive publicly available genomic cohorts of the METABRIC study were examined to delineate and compare their molecular landscape. Genetic and epigenetic alterations of key factors involved in EMT and potentially associated with the pathogenesis of the claudin-low phenotype were analyzed in the two groups. RESULTS: Claudin-low cancers displayed up-regulation of several core transcription factors of EMT at the mRNA level, compared with claudin-non-suppressed breast cancers. Global promoter DNA methylation was increased in both groups of triple-negative cancers and in claudin-low ER-positive cancers compared with the rest of ER-positive cancers. Histone modifier enzymes, including methyltransferases, demethylases, acetyltransferases and deacetylases displayed amplifications more frequently in claudin-non-suppressed triple-negative cancers than in claudin-low counterparts and the expression of some of these enzymes differed significantly between the two groups. CONCLUSION: Claudin-low and claudin-non-suppressed triple-negative breast cancers differ in their landscape of EMT core regulators and epigenetic regulators. These differences may be explored as targets for therapeutic interventions specific to the two groups of triple-negative breast cancers.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| 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".