Systematic Meta-Analysis of Published Transcriptomic Prognostic Signatures and Development of a Robust Multi-Cohort Prognostic Classifier for Triple-Negative Breast Cancer

10 Jul 20264 min read0 viewsVerified Feed

GIST (Key Takeaways)

Triple-negative breast cancer (TNBC) exhibits pronounced molecular heterogeneity, yet the majority of published transcriptomic prognostic signatures suffer from limited reproducibility and have not achieved clinical translation. We systematically benchmarked 62 published TNBC prognostic signatures across 6 independent cohorts (n=1,357) using a unified analytical framework spanning multiple scoring algorithms, survival endpoints, and threshold strategies.
While 17 signatures demonstrated consistent univariate prognostic associations, only 4 remained independently prognostic after adjustment for clinicopathological variables, and none achieved robustness across all analytical conditions-underscoring the fragility of existing classifiers. Leveraging genes with concordant survival associations across all 6 discovery cohorts, we identified a reproducible 15-gene directionally concordant gene set (DCGS) signature and distilled it into MetaSig-EFS, a 13-gene prognostic model optimized using a cohort-aware DeepSurv framework.
MetaSig-EFS demonstrated robust cross-cohort generalizability, achieving validation concordance indices of 0.89 in GSE19615 and 0.69 in JBordet, with corresponding 3- and 5-year time-dependent AUROCs of 0.89 and 0.96 in GSE19615 and 0.80 and 0.71 in JBordet, respectively, while retaining independent prognostic value across established TNBC molecular sub-typing systems.

Clinical Editorial

bioRxiv (Biomedical Preprints) published a clinical update in Research Highlights on 10 Jul 2026.

The item focuses on Systematic Meta-Analysis of Published Transcriptomic Prognostic Signatures and Development of a Robust Multi-Cohort Prognostic Classifier for Triple-Negative Breast Cancer.

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