Identification of a long non-coding RNA signature associated with cuproptosis for prognosis and immunotherapy response prediction in patients with lung adenocarcinoma.

Abstract

Background: Lung adenocarcinoma (LUAD), the most common histotype of lung cancer, exhibits high heterogeneity due to molecular variations. Cuproptosis is a newly discovered type of cell death that is linked to copper metabolism and long non-coding RNAs (lncRNAs) may play a significant role in this process. We conducted a comprehensive analysis of lncRNA related to cuproptosis and identified a CRLscore to predict the prognosis and immune landscape for LUAD patients.

Methods: The LUAD patient cohort obtained from TCGA database was divided into training and validation sets. A range of statistical methods were employed to identify lncRNAs associated with cuproptosis. Multivariate Cox regression was then utilized to develop the CRLscore, which was further used to construct and evaluate a nomogram. Additionally, we investigated the biological functions, gene mutations, and immune landscape.

Results: A CRLscore, comprising six cuproptosis-related lncRNAs, was developed to stratify patients into high- and low-risk groups. The CRLscore demonstrated its ability to independently predict prognosis in both the training set and the validation set. Utilizing the CRLscore, we constructed a nomogram that exhibited favorable predictive efficiency. Furthermore, the cuproptosis-related lncRNAs exhibited associations with important signaling pathways such as p53 signaling, MYC Targets V1, and G2M Checkpoint. Notably, the CRLscore displayed substantial differences in somatic mutations and immune landscape. Finally, qRT-PCR results showed the significant differential expression of five cuproptosis-related lncRNAs between LUAD and normal cells.

Conclusion: The CRLscore could serve as a potential prognostic indicator and may predict the response to immunotherapy in LUAD patients.