Identification of Potential Prognostic Value of Clock-related LncRNA with Immune Implications in Non-small Cell Lung Cancer

Abstract

Abstract Objective Our aim is to construct a prognostic model of clock-related lncRNAs for patients with non-small cell lung cancer (NSCLC) and evaluate its relationship with tumor immune microenvironment. Methods The data of 944 NSCLC cases were screened and obtained from the TCGA database. Circadian rhythm-related Gene Set (consisting of 70 clock-related genes) was identified using the GSEA website. Clock-related lncRNAs were obtained by co-expression analysis. The abundance of immune cell infiltrates in NSCLC patients was calculated using CIBERSORT. Clock-related lncRNAs risk scores were calculated via the Least Absolute shrinkage and Selection Operator (LASSO) penalized Cox regression analysis. Then we divided the 944 NSCLC cases into training set (473 cases) and validation set (471 cases) based on the median risk score. The independence risk factors for clinical pathological parameters and risk score were analyzed using the univariate and multivariate Cox regression analysis. We also explored the relationship between risk score and immune cell infiltration in NSCLC cases. Results A total of 12 clock-related lncRNAs were selected from the training set to calculate the risk score. Patients in the high-risk group had poor prognosis than patients in the low-risk group, which were both validated in the training set and validation set (P < 0.001, P < 0.05, respectively). The area under the curve (AUC) of risk score was 0.763 and 0.624, respectively. Multivariate Cox analysis showed that T stage, N stage, age, and clock-related lncRNAs risk score were independent risk factors for prognosis of patients with NSCLC. B Cell naive and Mast cells resting showed high invasion abundance in the low-risk groups (P < 0.01), while Macrophages M0, Macrophages M1 and Neutrophils cells showed high infiltration abundance in the high-risk groups (P < 0.01). Conclusions In conclusion, the risk score of 12 clock-related lncRNAs was identified as a prognostic biomarker for patients with NSCLC, and was significantly associated with the regulation of immune cell subtypes.