Prediction of prognosis and immunotherapy response with a robust immune-related lncRNA pair signature in lung adenocarcinoma

The tumor immune microenvironment plays essential roles in regulating inflammation, angiogenesis, immune modulation, and sensitivity to therapies. Here, we developed a powerful prognostic signature with immune-related lncRNAs (irlncRNAs) in lung adenocarcinoma (LUAD). We obtained differentially expressed irlncRNAs by intersecting the transcriptome dataset for The Cancer Genome Atlas (TCGA)-LUAD cohort and the ImmLnc database. A rank-based algorithm was applied to select top-ranking altered irlncRNA pairs for the model construction. We built a prognostic signature of 33 irlncRNA pairs comprising 40 unique irlncRNAs in the TCGA-LUAD cohort (training set). The immune signature significantly dichotomized LUAD patients into high- and low-risk groups regarding overall survival, which is likewise independently predictive of prognosis (hazard ratio = 3.580, 95% confidence interval = 2.451-5.229, P < 0.001). A nomogram with a C-index of 0.79 demonstrates the superior prognostic accuracy of the signature. The prognostic accuracy of the signature of 33 irlncRNA pairs was validated using the GSE31210 dataset (validation set) from the Gene Expression Omnibus database. Immune cell infiltration was calculated using ESTIMATE, CIBERSORT, and MCP-count methodologies. The low-risk group exhibited high immune cell infiltration, high mutation burden, high expression of CTLA4 and human leukocyte antigen genes, and low expression of mismatch repair genes, which predicted response to immunotherapy. Interestingly, pRRophetic analysis demonstrated that the high-risk group possessed reverse characteristics was sensitive to chemotherapy. The established immune signature shows marked clinical and translational potential for predicting prognosis, tumor immunogenicity, and therapeutic response in LUAD.