Abstract
BACKGROUND: Non-small cell lung cancer with homologous recombination deficiency (HRD) was revealed to have better response to immunotherapy. Long non-coding RNAs (lncRNAs) modulate multiple processes including HRD acting as potential biomarkers in tumors. The function of HRD-associated lncRNAs in lung cancer arouses our interests. METHODS: Two independent cohorts were enrolled containing 838 lung adenocarcinoma (LUAD) patients. HRD-associated lncRNAs were defined as the lncRNAs that were differential expressed in high-HRD group and low-HRD group which were classified in accordance with the HRD score. The least absolute shrinkage and selection operator cox regression was employed to construct a signature according to prognostic HRD-associated lncRNAs. The signature robustness was evaluated by using the prognosis analysis, multivariate-cox analysis, ROC curve, and nomogram. The participating pathways were estimated by gene set enrichment analysis and KEGG pathway analysis. The infiltration of immune cells was estimated by using xCell. The tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were both utilized for the prediction of immunotherapy response. RESULTS: Seventeen HRD-associated lncRNAs were screened to classify the LUAD patients into two groups with variant survival that inferior overall survival was found in high-risk patients comparing to those with low-risk. Our model not only was the independent prognostic factor in LUAD but also had better performance on the prognosis prediction when making a comparison with other clinical and molecular signatures. Additionally, the high-risk group was suggested to have increased genomic instability and less response to immunotherapy. CONCLUSION: A great predicative efficient prognostic signature was established based on 17 HRD-associated lncRNAs in LUAD. The signature might be the predictor for genomic instability and immunotherapy response in LUAD. Our findings provided new insight for the improvement of clinical stratification in LUAD.