Construction of an immune-related lncRNA signature pair for predicting oncologic outcomes and the sensitivity of drugs to treat adverse reactions to immunotherapy in lung adenocarcinoma

Abstract

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 pair (IRLPs) score for LUAD and identify the best drugs to treat immune-related adverse events (ir AEs). Methods Based on The Cancer Genome Atlas (TCGA) LUAD dataset, IRLPs were identified to construct an IRLPs scoring system by Cox regression and were validated in the Gene Expression Omnibus (GEO) dataset. Next, immune and molecular characteristics were explored in different IRLP subgroups. The “pRRophetic” package was used to predict the sensitivity of drugs used to treat ir AEs. Results A total of 477 LUAD patients in TCGA with gene expression and mutation data with complete clinicopathological features were found in our study and used as a training set. The study also included 318 patients from three GEO datasets. The IRLPs score was constructed based on eight IRLPs, and patients with a high IRLP risk score had a better overall survival (OS). 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 highest IRLP risk score. The high-risk group was found enriched in molecular changes in DNA and chromosomes, 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 drugs for ir AEs therapy.