Identification of immune-associated lncRNAs as a prognostic marker for lung adenocarcinoma.

Abstract

BackgroundLung adenocarcinoma (LUAD) accounts for the largest proportion of lung cancer patients and has the highest morbidity and mortality worldwide. Accumulating evidence shows that immune-associated long non-coding RNAs (lncRNAs) play a role in LUAD, although their predictive value for immunotherapy treatment and cancer-related death remains poorly investigated.MethodsGene expression profiles and clinical data were obtained from The Cancer Genome Atlas. We constructed a risk model by univariate and multivariate Cox regression and least absolute shrinkage and selection operator regression analysis and subsequently divided each sample into low- or high-risk category. Survival and receiver operating characteristic (ROC) analyses were applied to assess the prognostic value of the model. Additionally, immune and somatic mutation status were analysed between the two risk groups. Finally, the model was applied to pancreatic ductal adenocarcinoma (PDAC) samples to explore the applicability of the model in other cancers.ResultsWe obtained data from 499 LUAD patients and randomised the samples into a training set (N=351) and validation set (N=148) at a 7:3 ratio. We detected 7 immune-associated lncRNAs (AP000695.2, AC026355.2, LINC01843, ITGB1-DT, LINC01150, AL590226.1 and AC091185.1) that were applicable for establishing a risk signature. Survival analysis revealed that patients categorised in the high-risk group had shorter overall survival (OS) than those in the low-risk group. ROC analyses showed excellent AUC values in all data sets (>0.65 at 1, 3, and 5 years). Notably, ESTIMATE algorithm and analysis of PCA, (ss)GSEA, and somatic mutations revealed that the high-risk group had a stronger immunosuppressive status and a higher tumour mutation burden (TMB). Moreover, patients in the low-risk group responded better to immunotherapy due to higher levels of immune-checkpoint receptor genes and TLS-related genes. Our model using the 7 immune-associated lncRNAs showed similar applicability for PDAC patients.ConclusionsWe constructed a model for risk signatures based on 7 immune-associated lncRNAs and showed its prognostic value for identifying immune and somatic mutation characteristics in LUAD patients, which may assist clinical treatment plans and elucidate molecular mechanisms of LUAD immunity.