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Research Paper|Volume 16, Issue 4|pp 3531—3553

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

Hua Zhong1, Lijie Chang2, Shengbin Pei1, Yakun Kang1, Lili Yang1, Yifan Wu1, Nuo Chen1, Yicheng Luo1, Yixiao Zhou1, Jiaheng Xie3, Yiqin Xia1
  • 1Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
  • 2Department of Neonatal Intensive Care Unit, The Second Affiliated Hospital, Anhui Medical University, Hefei, China
  • 3Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
* Equal contribution and shared the first authorship
Received: July 13, 2023Accepted: January 9, 2024Published: February 14, 2024

Copyright: © 2024 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.