AUTHOR=Hua Xin , Zhu Qi-Wei , Zhang Yi-Nuan , Cao Lu , Wang Meng-Di , Gao Yun-Sheng , Chen Jia-Yi TITLE=The prognostic significance of human ovarian aging-related signature in breast cancer after surgery: A multicohort study JOURNAL=Frontiers in Immunology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1139797 DOI=10.3389/fimmu.2023.1139797 ISSN=1664-3224 ABSTRACT=Abstract Background: Recent studies indicate that ovarian aging is strongly associated with the risk of breast cancer, but its prognostic impact on breast cancer is understudied. We performed a multicohort genetic analysis to explore its prognostic values and biological functional features in breast cancer. Methods: The expression and clinicopathological data involving 3366 patients from the TCGA cohort, the METABRIC cohort and the GSE86166 cohort were analyzed. A total of 290 ovarian ageing-related genes (OARGs) were included for prognostic model establishment. Functional mechanisms analysis, drug sensitivity, and immune cell infiltration were investigated by bioinformation methods. Results: An eight OARG-based signature was established and validated in independent cohorts. Two risk subgroups of patients with distinct survival outcomes were identified by the OARG-based signature. A nomogram model with good predictive performance was developed by integrating OARG risk score with clinicopathological factors. Moreover, the OARG-based signature was correlated with DNA damage repair and immunomodulatory function effects. Patients in the low-risk subgroup are sensitive to traditional chemo, endocrine, and targeted agents (doxorubicin, tamoxifen, lapatinib, etc.) and some novel molecularly targeted drugs (sunitinib, pazopanib, etc.). Conclusions: This genetic association research proposed a comprehensive analysis method for breast cancer based on OARG expression patterns, which could precisely predict clinical outcomes and drug sensitivity in breast cancer.