ArticleTranslational cancer research2026
Development and validation of a herb-related gene signature for prognosis prediction and therapeutic response assessment in breast cancer.
Article in Translational cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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4 authors.
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Abstract
Background: Breast cancer is a highly heterogeneous disease, and there is a continuing need for robust prognostic tools that can also inform therapeutic strategies. This study aimed to develop a novel prognostic signature for breast cancer by leveraging the multi-target philosophy of traditional Chinese medicine (TCM). Methods: We systematically analyzed 221 TCM prescriptions for breast cancer to identify potential herb-related targets. A 20-gene herb-related risk score (HRS) was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in The Cancer Genome Atlas (TCGA) breast cancer cohort (n=1,097). The model's prognostic performance was validated in three independent cohorts: Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n=1,466), GSE20685 (n=327), and GSE10886 (n=226). We further investigated the association of the HRS with the tumor immune microenvironment and potential drug sensitivity using bioinformatics algorithms. Results: The HRS served as an independent prognostic factor for overall survival (OS) [TCGA: hazard ratio (HR) =2.03, 95% confidence interval (CI): 1.25-3.30, P=0.004; METABRIC: HR =1.82, 95% CI: 1.59-2.10, P<0.001]. Time-dependent receiver operating characteristic analysis demonstrated consistent prognostic discrimination, with an area under the curve (AUC) for 3-year OS of 0.709 (95% CI: 0.657-0.761) in the TCGA cohort. A high HRS was significantly associated with an immunosuppressive microenvironment and reduced predicted response to immune checkpoint blockade. Furthermore, the signature identified several compounds (e.g., sirolimus, temsirolimus) with potential heightened sensitivity in high-risk patients. Conclusions: This study developed and validated a novel TCM-derived gene signature that reliably stratifies breast cancer patients into distinct risk groups and is independently prognostic. While its clinical utility requires extensive validation in prospective studies before it can inform patient management, this novel gene signature may serve as a potential tool for individualized risk assessment and prognosis prediction, while also generating compelling hypotheses for guiding immunotherapy and targeted therapy strategies, contributing to the ongoing exploration of precision oncology in breast cancer.
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