Cuproptosis-related lncRNAs potentially predict prognosis and therapy sensitivity of breast cancer

Xiwen Wu; Ying Zhang; Gehao Liang; Huizhen Ye

doi:10.3389/fphar.2023.1199883

Cuproptosis-related lncRNAs potentially predict prognosis and therapy sensitivity of breast cancer

Front Pharmacol. 2023 Jul 17:14:1199883. doi: 10.3389/fphar.2023.1199883. eCollection 2023.

Authors

Xiwen Wu¹, Ying Zhang², Gehao Liang³, Huizhen Ye²

Affiliations

¹ Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
² Staff and Faculty Clinic, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
³ Department of Breast Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Abstract

Background: Cuproptosis-related lncRNAs regulate the biological functions of various cancers. However, the role of cuproptosis-related lncRNAs in breast cancer remains unclear. In this study, we investigated the biological functions and clinical applications of cuproptosis-related lncRNAs in breast cancer. Methods: The Cancer Genome Atlas (TCGA) database and the GSE20685 dataset were used for screening cuproptosis-related lncRNAs. Colony formation and CCK-8 kit assays were performed for detecting the proliferative function of cuproptosis-related lncRNAs, whereas wound healing, migration, and invasion assays were performed for detecting the metastatic regulation of cuproptosis-related lncRNAs in breast cancer. Finally, a prognostic cuproptosis-related lncRNA model was constructed using LASSO Cox regression analysis for detecting survival and sensitivity to conventional treatment (endocrine therapy, chemotherapy, and radiotherapy) and novel therapy (PARP and CDK4/6 inhibitors). Results: In this study, we screened six cuproptosis-related lncRNAs associated with the survival of patients with breast cancer. Biofunctional experiments indicated that cuproptosis-related lncRNAs play essential roles in regulating the proliferation and metastasis of breast cancer cells. Finally, we applied a model of six cuproptosis-related lncRNAs to classify the patients into high- and low-risk groups. High-risk group patients exhibited worse survival rates (p < 0.001) and lower sensitivity to chemotherapy, endocrine therapy, and radiation therapy. Compared with high-risk patients, low-risk patients exhibited a lower expression of CDK4/6 inhibitor-resistant biomarkers (CCNE1, E2F1, and E2F2) and PARP inhibitor-resistant biomarkers (BRCA1/BRCA2), indicating that patients in the low-risk group were more suitable for PARP inhibitor and CDK4/6 inhibitor application. Conclusion: Cuproptosis-related lncRNAs are essential for regulating the biological functions of breast cancer, and they have the potential to predict prognosis and sensitivity of breast cancer to various therapies.

Keywords: biological functions; breast cancer; clinical practice; cuproptosis; lncRNA.

Grants and funding

The authors greatly acknowledge the financial support from the National Natural Science Foundation of China (Grant number: 82203463).