Construction of an immune-related lncRNA signature pair for predicting oncologic outcomes and the sensitivity of immunosuppressor in treatment of lung adenocarcinoma.

Background: Although immunotherapy has shown clinical activity in lung adenocarcinoma (LUAD), LUAD prognosis has been a perplexing problem. We aimed to construct an immune-related lncRNA pairs (IRLPs) score for LUAD and identify what immunosuppressor are appropriate for which group of people with LUAD.

Methods: Based on The Cancer Genome Atlas (TCGA)-LUAD cohort, IRLPs were identified to construct an IRLPs scoring system by Cox regression and validated in the Gene Expression Omnibus (GEO) dataset using log-rank test and the receiver operating characteristic curve (ROC). Next, we used spearman's correlation analysis, t-test, signaling pathways analysis and gene mutation analysis to explore immune and molecular characteristics in different IRLP subgroups. The "pRRophetic" package was used to predict the sensitivity of immunosuppressant.

Results: The IRLPs score was constructed based on eight IRLPs calculated as 2.12 × (MIR31HG|RRN3P2) + 0.43 × (NKX2-1-AS1|AC083949.1) + 1.79 × (TMPO-AS1|LPP-AS2) + 1.60 × (TMPO-AS1|MGC32805) + 1.79 × (TMPO-AS1|PINK1-AS) + 0.65 × (SH3BP5-AS1|LINC01137) + 0.51 × (LINC01004|SH3PXD2A-AS1) + 0.62 × (LINC00339|AGAP2-AS1). Patients with a lower IRLPs risk score had a better overall survival (OS) (Log-rank test P  < 0.001, P  = 0.017, P  = 0.027) and similar results were observed in the AUCs of TCGA dataset and GEO dataset (AUC  = 0.777, AUC  = 0.685, AUC  = 0.733, AUC  = 0.680). Immune score (Cor = -0.18893, P < 0.001), stoma score (Cor = -0.24804, P < 0.001), and microenvironment score (Cor = -0.22338, P < 0.001) were significantly decreased in the patients with the higher IRLP risk score. The gene set enrichment analysis found that high-risk group enriched in molecular changes in DNA and chromosomes signaling pathways, and in this group the tumor mutation burden (TMB) was higher than in the low-risk group (P = 0.0015). Immunosuppressor methotrexate sensitivity was higher in the high-risk group (P = 0.0052), whereas parthenolide (P < 0.001) and rapamycin (P = 0.013) sensitivity were lower in the high-risk group.

Conclusions: Our study established an IRLPs scoring system as a biomarker to help in the prognosis, the identification of molecular and immune characteristics, and the patient-tailored selection of the most suitable immunosuppressor for LUAD therapy.