Research Paper
A novel cuproptosis-associated immune risk model for prediction of prognosis and response to immunotherapy in triple-negative breast cancer
- 1 Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
- 2 Division of Head and Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610000, Sichuan Province, China
- 3 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing 100000, China
Received: July 4, 2023 Accepted: October 17, 2023
https://doi.org/10.18632/aging.205223How to Cite
Copyright: © 2023 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cuproptosis is closely associated with tumor progression and plays a role in tumor immunity. However, there is a lack of sufficient research on establishing a cuproptosis and immune-related risk model for predicting the prognosis and drug sensitivity of triple-negative breast cancer (TNBC). In this study, we collected clinical and gene expression data of TNBC patients from the TCGA and GEO databases. Based on cuproptosis-related genes, we identified two distinct cuproptosis patterns associated with immune response through consensus clustering and enrichment analyses. Thus, we constructed a prognostic cuproptosis-associated immune signature (CIS) in the TCGA-TNBC cohort and validated its predictive capacity in the GSE81540 and GSE58812 cohorts. TNBC patients with a high CIS exhibited significantly worse outcomes and higher rates of immune cell infiltration. Conversely, patients in the low-CIS group exhibited an immunosuppressive phenotype and potentially reduced sensitivity to immunotherapy. Furthermore, we predicted potential therapeutic agents for the low-CIS group and validated the levels of representative signature genes in cell lines and clinical samples. In all, We developed a novel risk model with cuproptosis and immune-related genes to predict OS and characterized immune microenvironment, and drug sensitivity, which might facilitate individual treatment of TNBC patients.
Abbreviations
TNBC: triple-negative breast cancer; CIS: cuproptosis-associated immune signature; ICBs: immune checkpoint blockades; TILs: tumor-infiltrating lymphocytes; PFS: progression-free survival; DEGs: differentially expressed genes; CIRGs: cuproptosis and immune-related genes; AUC: area under the curve; ROC: receiver operating characteristic; TILs: tumor-infiltrating lymphocytes.