Development and validation of the potential biomarkers based on m6A-related lncRNAs for the predictions of overall survival in the lung adenocarcinoma and differential analysis with cuproptosis

Abstract

Background: The treatment and prognosis of lung adenocarcinoma (LUAD) remains a challenge. The study aimed to conduct a systematic analysis of the predictive capacity of N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) in the prognosis of LUAD.

Methods: 594 samples were totally selected from a dataset from The Cancer Genome Atlas. The identification of prognostic m6A-related lncRNAs were performed by Pearson correlation analysis and Cox regression analysis. Systematic analyses, including cluster analysis, survival analysis, and immuno-correlated analysis, were conducted. A prognosis model was built from the optimized subset of m6A-related lncRNAs. The assessment of model was performed by survival analysis, and receiver operating characteristic (ROC) curve. Finally, the risk score of patients with LUAD calculated by the prognosis model was implemented by the analysis of Cox regression. Differential analysis was for further evaluation of the cuproptosis-related genes in two risk sets.

Results: These patients were grouped into two clusters according to the expression levels of 22 prognostic m6A-related lncRNAs. The patients with LUAD in cluster 2 was significantly worse in the overall survival (OS) (P = 0.006). Three scores calculated by the ESTIMATE methods in cluster 2 were significantly lower. After the least absolute shrinkage and selection operator algorithm, 10 prognostic m6A-related lncRNAs were totally selected to construct the final model to obtain the risk score. Then the area under the ROC curve of the prognosis model for 1, 3, and 5-year OS was 0.767, 0.709, and 0.736 in the training set, and 0.707, 0.691, and 0.675 in the test set. The OS of the low-risk cohort was significantly higher than that of the high-risk cohort in both the training set (P < 0.001) and test set (P < 0.001). After the analysis of Cox regression, the risk score [Hazard ratio (HR) = 5.792; P < 0.001] and stage (HR = 1.576; P < 0.001) were both considered as independent indicators of prognosis for LUAD. The expression levels of five cuproptosis-related genes were significantly different in two risk sets.

Conclusions: The study constructed a predictive model for the OS of patients with LUAD and these OS-related m6A-lncRNAs might have potential roles in LUAD progression.

Keywords: Biomarker; Long non-coding RNA; Lung adenocarcinoma; N6-methyladenosine; Prognosis.