Characterization of Cuproptosis-related LncRNA Landscape for Predicting the Prognosis and Aiding Immunotherapy in Lung Adenocarcinoma Patients

Cuproptosis is a newly discovered mechanism of regulated cell death, which serves as a novel target for cancer therapy. Long non-coding RNAs (lncRNAs) play an important role in the initiation and progression of cancer cells; however, the relationship between cuproptosis and lncRNAs in tumorigenesis and cancer treatment has not been well established in lung adenocarcinoma (LUAD). Thus, it is important to clarify and characterize the cuproptosis-related lncRNA landscape in LUAD. In this study, cuproptosis-related lncRNAs was screened by Pearson correlation analysis. Then, univariate, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression were conducted to identify 6 cuproptosis-related lncRNAs (AC090541.1, AC009226.1, NIFK-AS1, AC027097.2, AC026355.2, and AC106028.2) which were used to construct a cuproptosis-related lncRNA signature (CRLS). Multi-dimensional assessments including Kaplan-Meier analysis, receiver operating characteristics (ROC) curves, and principal component analysis (PCA) verified that the CRLS could reliably predict the prognosis and survival of LUAD patients. We further compared the immune cell infiltration, somatic mutation landscape, and functional enrichment pathways between the high and low CRLS groups. Patients with low CRLS scores had prolonged survival and were sensitive to immunotherapy, whereas patients with high CRLS scores might benefit better from chemotherapy. We further analyzed the individualized immunotherapeutic strategies and the candidate compounds for the potential clinical treatment. Moreover, the expression level of these 6 lncRNAs was examined experimentally in vitro by using quantitative real-time polymerase chain reaction (RT-qPCR). Additionally, one of the significantly differentially expressed lncRNAs, NIFK-AS1, was confirmed to suppress the proliferation and migration of LUAD by Cell Counting Kit-8 Assays (CCK-8), wound healing assay, and colony formation assays. Taken together, we established a CRLS that might be a promising tool for predicting the prognosis, guiding individualized treatment, and serving as a promising therapeutic target for patients with LUAD.