A novel pyroptosis related genes signature for predicting prognosis and estimating tumor immune microenvironment in lung adenocarcinoma

BACKGROUND: Pyroptosis is a newly found form of programmed cell death, accompanied by inflammatory response as well as immune response. Here, the specific function and prognosis predictive of pyroptosis-related genes (PRGs) were systematically explored in lung adenocarcinoma (LUAD). METHODS: The gene expression data and corresponding clinical information of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), and the expression level of PRGs was identified between normal and tumor tissues. Furthermore, univariate Cox proportional hazards regression was conducted to filter the PRGs related to overall survival, and least absolute shrinkage and selection operator (LASSO) regression was subsequent employed to establish the PRGs risk model. Besides, the correlation of risk score with patients’ clinical features, tumor mutational burden (TMB) as well as tumor microenvironment (TME) was also investigated. RESULTS: A total of 5 PRGs (NLRC4, NLRP1, NLRP3, NOD1, PLCG1, and BAK1) was used to establish the risk prognostic model. According the median value of risk score, all the patients were classified into low- and high-risk score group. Kaplan-Meier analysis indicted that the LUAD patients in low-risk group exhibited a better survival outcome compared the patients in high-risk group (P<0.001). After adjusting for age, gender, and clinical stage, the risk score was also considered as and independent risk factor affecting the overall survival of LUAD patients (HR =2.949, 95% CI: 1.762–4.937). Moreover, low-risk score group exhibited a higher Immune score and lower Tumor purity compared with high-risk score group. ssGSEA results proved that the enrichment scores of most immune cells and immune related signal pathway in low-risk score group was significant higher than that in high-risk score group. In addition, the PRGs risk score was also positive correlated with TMB in LUAD tissues. CONCLUSIONS: In this study, a novel prognostic model based on PRGs was constructed and used to predict the survival outcome of LUAD patients. In addition, the PRGs risk signature was also associated with TMB and anti-tumor immune environment. The induction of pyroptosis inside tumors might be considered a potential strategy in cancer treatments.