| evidence-b2-doi-10-3389-fonc-2025-1538574-1 | KF1: The TNBC single-cell series revealed BRCA1-associated differences in annotated tumor immune and stromal states. | Observed four versus four specimens allow exploratory group comparison; 32,386 cells are nested within eight donors and are not independent patients. | The TNBC single-cell series revealed BRCA1-associated differences in annotated tumor immune and stromal states. TNBC samples: 4 BRCA1-MT and 4 BRCA1-WT; QC-retained cells: 32,386; 18,182 mutant-group and 14,204 wild-type-group; Broad annotated lineages: 7 principal populations | Observed four versus four specimens allow exploratory group comparison; 32,386 cells are nested within eight donors and are not independent patients. | Observed four versus four specimens allow exploratory group comparison; 32,386 cells are nested within eight donors and are not independent patients. | PMC12401915: Methods Data acquisition and processing (s2_1); Results The single-cell atlas of BRCA1 MT and BRCA1 WT samples (s3_1); Figure 1A–D. | KF1 |
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| evidence-b2-doi-10-3389-fonc-2025-1538574-2 | KF2: T-cell exhaustion and dendritic/macrophage-associated expression programs differed by BRCA1 group. | State labels and inferred scores are descriptive transcriptomic signatures; lineage transitions and immunotherapy effectiveness cannot be inferred directly. | T-cell exhaustion and dendritic/macrophage-associated expression programs differed by BRCA1 group. Comparison: BRCA1-WT versus BRCA1-MT single-cell specimens; CD4/CD8 states: Treg, Tex and other computationally annotated subsets; Intercellular readouts: Pseudotime and inferred spatial signaling, not direct lineage tracing | State labels and inferred scores are descriptive transcriptomic signatures; lineage transitions and immunotherapy effectiveness cannot be inferred directly. | State labels and inferred scores are descriptive transcriptomic signatures; lineage transitions and immunotherapy effectiveness cannot be inferred directly. | PMC12401915: Results T cells in BRCA1-WT specimens (s3_2); Activated TAMs and tolerogenic DCs (s3_3); Figures 2–3 and supplemental Figures S3–S5. | KF2 |
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| evidence-b2-doi-10-3389-fonc-2025-1538574-3 | KF3: Distinct CAF states and ISG15-associated molecular programs were prioritized using multi-modal data. | Relative enrichment, pseudotime, spatial co-localization and proteomic associations do not prove BRCA1 regulates CAF differentiation through a causal ISG15 pathway. | Distinct CAF states and ISG15-associated molecular programs were prioritized using multi-modal data. CAF state trend: myCAF associated with BRCA1-WT; iCAF associated with BRCA1-MT; Spatial observation: 4 BRCA1-WT spatial samples, not a direct genotype-matched spatial comparison; Paired proteomics: 9 tumor/adjacent-tissue pairs; Marker: ISG15 associated with myCAF enriched signatures | Relative enrichment, pseudotime, spatial co-localization and proteomic associations do not prove BRCA1 regulates CAF differentiation through a causal ISG15 pathway. | Relative enrichment, pseudotime, spatial co-localization and proteomic associations do not prove BRCA1 regulates CAF differentiation through a causal ISG15 pathway. | PMC12401915: Results BRCA1-driven CAF reprogramming (s3_6), Multi-scale analysis pinpointed ISG15 (s3_8), ISG15-driven predictor (s3_9); Figures 5–8; Methods high-sensitivity label-free proteomics (s2_11) and supplied DataSheet1.doc Supplementary Methods. | KF3 |
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| evidence-b2-doi-10-3389-fonc-2025-1538574-4 | KF4: The ICI response classifier showed modest retrospective discrimination in treatment cohorts from other cancers. | The held-out subsets come from a mixed-cancer model-selection pipeline; the study states it lacks an ICI-treated TNBC validation cohort. | The ICI response classifier showed modest retrospective discrimination in treatment cohorts from other cancers. Pooled cohort definition: Four cohorts combining to 661 records for 80:20 model development/evaluation; Chosen approach: K-nearest neighbors, selected among the models by validation performance; Validation ROC AUC: 0.60 (95% CI 0.51–0.69); Testing ROC AUC: 0.61 (95% CI 0.51–0.71) | The held-out subsets come from a mixed-cancer model-selection pipeline; the study states it lacks an ICI-treated TNBC validation cohort. | The held-out subsets come from a mixed-cancer model-selection pipeline; the study states it lacks an ICI-treated TNBC validation cohort. | PMC12401915: Methods Reconstruction of the ICI response predictor (s2_10); Results Construction of an ISG15-driven predictive system (s3_9); Figure 8D–G. Paper text inconsistency: Methods mentions 13 cohorts (n=829); Results mentions 12. | KF4 |
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| evidence-b2-doi-10-3389-fonc-2025-1538574-5 | KF5: High predicted response group correlated with immune-signature and selected survival patterns but does not establish TNBC treatment benefit. | The correlation in METABRIC is not treated ICI response and the TCGA TNBC survival comparison did not reach nominal significance. | High predicted response group correlated with immune-signature and selected survival patterns but does not establish TNBC treatment benefit. METABRIC overall survival: Reported nominal P<0.05 by predicted response group; TCGA TNBC overall survival: P=0.182; not statistically significant; TIDE interpretation: Computational exclusion and dysfunction estimates, not observed ICI response | The correlation in METABRIC is not treated ICI response and the TCGA TNBC survival comparison did not reach nominal significance. | The correlation in METABRIC is not treated ICI response and the TCGA TNBC survival comparison did not reach nominal significance. | PMC12401915: Results Construction of an ISG15-driven predictive system for ICI response (s3_9); Figure 8H–K; Discussion (s4), paragraph explicitly stating no ICI-treated TNBC validation. | KF5 |
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