A New Risk Score Model Based on Pyrogenic Signatures for the Prediction of Survival and Immune Microenvironment Features in Lung Adenocarcinoma

Abstract

Lei Zhao,1 Longfei Wang,2 Tao Guo,1 Chundong Gu,1 Jinna Wang3 1Thoracic Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China; 2Thoracic Surgery, Ningbo First Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 3Oncology Department, Dalian Friendship Hospital, Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: Chundong Gu, Thoracic Surgery, the First Affiliated Hospital of Dalian Medical University, 222 Postal Code, Zhongshan Road, Dalian, Liaoning Province, 116011, People’s Republic of China, Tel: [phone], Fax [phone], Email [email protected] Jinna Wang, Oncology Department, Dalian Friendship Hospital, 838 Plaza, Zhongshan District, Taipei, Dalian, Liaoning Province, 116100, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: Lung adenocarcinoma (LUAD) accounts for about 40– 50% of all lung cancer cases with poor prognoses. Pyroptosis plays important roles in tumor development and anti-tumor processes. This study aims to investigate the prognostic value of pyroptosis-related genes in survival and tumor immune microenvironment (TIME) in LUAD.Patients and Methods: Three datasets were collected, of which 59 normal samples and 513 LUAD samples as experimental group, 163 LUAD samples for validation analysis, and 43 non-small cell lung cancer (NSCLC) samples included in the immunotherapy cohort. A total of 33 pyrolysis-related genes were included in univariate Cox regression analysis. Five pyroptosis-related genes, including NLRC4, NLRP1, NOD1, PLCG1 and CASP9 were screened using Lasso to construct a pyroptosis-related risk score model. Functional enrichment and immune microenvironment analyses were performed. Another 5 tissue samples of LUAD patients were collected for qRT-PCR validation.Results: According to the median risk score, the samples were divided into high-risk group and low-risk group, and the immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. Then, a nomogram was established based on clinical characteristics and risk score, which demonstrated high accuracy in 1-year OS. The risk score was significantly correlated with overall survival, immune-cell infiltration, and tumor mutation burden (TMB). qRT-PCR results showed that the expression of pyroptosis-related genes in tissues of LUAD patients was consistent with the trend in the experimental group.Conclusion: The risk score model may predict the overall survival of LUAD patients with good accuracy. Our results also demonstrate effectiveness in evaluating the response to immunosuppressive therapy, and may help improve the overall prognosis and treatment outcome of LUAD.Keywords: pyroptosis related gene, lung adenocarcinoma, risk score model, immune microenvironment infiltration

Keywords

• pyroptosis related gene
• lung adenocarcinoma
• risk score model
• immune microenvironment infiltration.