Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer

Xinyu Liu; Lei Zhou; Minghui Gao; Shuhong Dong; Yanan Hu; Chunjie Hu

doi:10.3389/fgene.2022.989646

Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer

Front Genet. 2022 Sep 20:13:989646. doi: 10.3389/fgene.2022.989646. eCollection 2022.

Authors

Xinyu Liu^{1

2}, Lei Zhou³, Minghui Gao^{1

2}, Shuhong Dong^{1

2}, Yanan Hu^{1

2}, Chunjie Hu^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
² NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, China.
³ Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Background: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs (lncRNAs) as a reference for individualized clinical treatment. Methods: A total of seven cuproptosis-related lncRNAs closely related to the prognosis of patients with CC were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator regression analysis in the training set. The predictive performance of the signature was evaluated by Kaplan-Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, and univariate and multivariate Cox analyses. Functional enrichment analysis and single-sample gene set enrichment analysis were conducted to explore the potential mechanisms of the prognostic signature, and a lncRNA-microRNA-mRNA network was created to investigate the underlying regulatory relationships between lncRNAs and cuproptosis in CC. The associations between the prognostic signature and response to immunotherapy and targeted therapy were also assessed. Finally, the prognostic value of the signature was validated using the CC tissues with clinical information in my own center. Results: A prognostic signature was developed based on seven cuproptosis-related lncRNAs, including five protective factors (AL441992.1, LINC01305, AL354833.2, CNNM3-DT, and SCAT2) and two risk factors (AL354733.3 and AC009902.2). The ROC curves confirmed the superior predictive performance of the signature compared with conventional clinicopathological characteristics in CC. The ion transport-related molecular function and various immune-related biological processes differed significantly between the two risk groups according to functional enrichment analysis. Furthermore, we discovered that individuals in the high-risk group were more likely to respond to immunotherapy and targeted therapies including trametinib and cetuximab than those in the low-risk group. Finally, CC tissues with clinical data from my own center further verify the robustness of the seven-lncRNA risk signature. Conclusion: We generated a cuproptosis-related lncRNA risk signature that could be used to predict prognosis of CC patients. Moreover, the signature could be used to predict response to immunotherapy and chemotherapy and thus could assist clinicians in making personalized treatment plans for CC patients.

Keywords: cervical cancer; cuproptosis; immunotherapy; lncRNA; prognosis; targeted therapy.