Cuproptosis-Related lncRNAs Signature Predicts Prognosis and Chemotherapeutic Response of Patients with Lung Adenocarcinoma

Abstract

Cuproptosis is a lipoylated tricarboxylic acid (TCA) cycle proteins-mediated novel cell death. Long non-coding RNAs (lncRNAs) involved in multiple cell death and lung adenocarcinoma (LUAD) process and might be as a signature to predict prognosis and therapeutic response of patients. However, the predictive performance of cuproptosis-related lncRNAs (CuRLs) is still unclear in LUAD. Here, we constructed a 13-cuproptosis-related-lncRNA signature (CuRLsig) through LASSO penalized Cox regression analysis to separate patients into low- and high-risk groups. The low-risk group has longer overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) compared to high-risk LUAD patients. The CuRLsig-derived risk score was independent of other clinical variables (age, gender, and stage) in predicting outcomes and further had better predictive ability to predict the prognosis of LUAD patients compared with other lncRNA model. Functionally, the high-risk group was associated with proteasome, spliceosome, respiratory chain and cyclin complex, p53 signaling pathway and DNA damage and repair pathways. Additionally, the CuRLsig-derived risk score can properly measure chemotherapeutic sensitivity to low- and high-risk LUAD patients. These results demonstrated that CuRLsig could be a powerful predictor and providing novel insights into the prognosis and treatment of LUAD patients.