Identification of Fatty Acid Metabolism-Related lncRNAs as Biomarkers for Clinical Prognosis and Immunotherapy Response in Patients With Lung Adenocarcinoma.

Abstract

Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with poor prognosis. Fatty acid metabolism is associated with cancer progression and a poor prognosis. We searched for long noncoding RNAs (lncRNAs) associated with fatty acid metabolism to predict the overall survival (OS) of patients with LUAD. We obtained lncRNA expression profiles and clinical follow-up data related to fatty acid metabolism in patients with LUAD from The Cancer Genome Atlas and Molecular Signatures database. Patients were randomly divided into training, experimental, and combination groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression models were used to construct fatty acid metabolism-related prognostic markers, Kaplan-Meier analysis was used to compare the prognosis of each group, and receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of the prognostic model. We used the pRRophetic algorithm to assess the treatment response based on the half-maximal inhibitory concentration (IC50) of each sample in the Genomics of Cancer Drug Sensitivity (GDSC) database. A fatty acid metabolism-related prognostic marker containing seven lncRNAs was constructed to predict OS in LUAD. In the training, test and combination groups, the patients were divided into high- and low-risk groups according to a formula. K–M analysis showed that patients in the high-risk group had poorer prognosis, with significant differences in the subgroup analysis. ROC analysis showed that the predictive ability of the model was more accurate. A clinical prediction nomogram combining lncRNA and clinical features was constructed to accurately predict OS and had high clinical application value. Therapeutics were screened based on the IC50 values of each sample in the GDSC database. We found that A.443654, AUY922, AZ628, A.770041, AZD.0530, AMG.706, and AG.014699 were more effective in high-risk patients. We constructed a 7-lncRNA prognostic model to predict the OS of patients with LUAD. In addition, the predictive nomogram model based on our established seven fatty acid metabolism-related lncRNA signatures provides better clinical value than that of the traditional TNM staging system in predicting the prognosis of patients with LUAD and presents new insights for personalized treatment.