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Research Paper|Volume 16, Issue 15|pp 11553—11567

The deubiquitinating enzymes-related signature predicts the prognosis and immunotherapy response in breast cancer

Youyuan Deng1, Jingyong Li1, Ye He1, Dou Du2, Zhiya Hu3, Chao Zhang1, Qishuo Rao1, Yiping Xu1, Jianguo Wang1, Ke Xu4,5
  • 1Department of General Surgery, Xiangtan Central Hospital, Xiangtan 410000, Hunan, P.R. China
  • 2Department of Pathology, Xiangtan Central Hospital, Xiangtan 410000, Hunan, P.R. China
  • 3Department of Pharmacy, The Third Hospital of Changsha, Changsha 410000, Hunan, P.R. China
  • 4Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan, P.R. China
  • 5Clinical Medical College, Chengdu Medical College, Chengdu 610500, Sichuan, P.R. China
Received: October 31, 2023Accepted: May 30, 2024Published: July 9, 2024
https://doi.org/10.18632/aging.206010

Copyright: © 2024 Deng 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

Background: Breast cancer is a prevalent disease that has a dismal prognosis for patients and a bad outlook for treatments. Ubiquitination is a reversible biological process that regulates protein production and degradation, as well as plays a vital role in protein transport, localization, and biological activity.

Methods: We obtained the breast cancer patient sample data and used a machine learning technique to create a novel index called Deubiquitinating enzyme related index (DUBRI) by gathering genes associated to deubiquitinating enzymes. Based on DUBRI, we systematically analyze patients’ prognosis, clinical characteristics, tumor immune microenvironment, chemotherapy response and immunotherapy response. Finally, the function of OTUB2 was explored in breast cancer cells.

Results: DUBRI, which consists of five deubiquitinating enzyme genes (OTUB2, USP41, MINDY2, YOD1, and PSMD7), is a reliable predictor of survival in breast cancer patients. We found that the high DUBRI group presented higher levels of immune cell infiltration. We performed molecular docking prediction of core target proteins in deubiquitinating enzymes. In vitro experiments verified that knockdown of OTUB2 could inhibit the proliferation and migration of breast cancer.

Conclusions: The DUBRI discovered in this research may effectively evaluate the outlook of breast cancer patients and identify groups of patients who would gain advantages from immunotherapy, offering vital knowledge for the future targeted treatment of breast cancer patients.