Senescence-related genes analysis in breast cancer reveals the immune microenvironment and implications for immunotherapy

乳腺癌衰老相关基因分析揭示免疫微环境及其对免疫治疗的意义

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作者:Hua Zhong, Lijie Chang, Shengbin Pei, Yakun Kang, Lili Yang, Yifan Wu, Nuo Chen, Yicheng Luo, Yixiao Zhou, Jiaheng Xie, Yiqin Xia

Abstract

Despite the advent of precision therapy for breast cancer (BRCA) treatment, some individuals are still unable to benefit from it and have poor survival prospects as a result of the disease's high heterogeneity. Cell senescence plays a crucial role in the tumorigenesis, progression, and immune regulation of cancer and has a major impact on the tumor microenvironment. To find new treatment strategies, we aimed to investigate the potential significance of cell senescence in BRCA prognosis and immunotherapy. We created a 9-gene senescence-related signature. We evaluated the predictive power and the role of signatures in the immune microenvironment and infiltration. In vitro tests were used to validate the expression and function of the distinctive critical gene ACTC1. Our risk signature allows BRCA patients to receive a Predictive Risk Signature (PRS), which may be used to further categorize a patient's response to immunotherapy. Compared to conventional clinicopathological characteristics, PRS showed strong predictive efficacy and precise survival prediction. Moreover, PRS subgroups were examined for altered pathways, mutational patterns, and possibly useful medicines. Our research offers suggestions for incorporating senescence-based molecular classification into risk assessment and ICI therapy decision-making.

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