PERP May Affect the Prognosis of Lung Adenocarcinoma by Inhibiting Apoptosis

Abstract

Zhongxiang Liu,1,* Shuhua Han,2,* Yuhong Luo,3,* Zhangyan Zhao,4 Lingyu Ni,5 Linlin Chai,6 Haicheng Tang4 1Department of Pulmonary and Critical Care Medicine, the Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, the First Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, 224000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People’s Republic of China; 3College of Life Science and Technology, Guangxi University, Nanning, 530004, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People’s Republic of China; 5China School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210046, People’s Republic of China; 6Department of Pathology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, The First Affiliated Hospital of Jiangsu Vocational College of Medicine, Yancheng, 224000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linlin Chai, Department of Pathology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China, Email [email protected] Haicheng Tang, Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Fudan University, 2901, Caolang Road, Jinshan District, Shanghai, 201508, People’s Republic of China, Email [email protected]: PERP, a member of the peripheral myelin protein gene family, is a new therapeutic target in cancer. The relationships between PERP and immune cell infiltration in lung cancer have not been studied. Therefore, the role of PERP in the tumour microenvironment (TME) of lung cancer needs to be further explored.Methods: In this study, we explored the association between PERP expression and clinical characteristics by analysing data from the TCGA database. Cox regression and Kaplan‒Meier methods were used to investigate the relationship between the expression of PERP and overall survival in patients with lung adenocarcinoma (LUAD). The relationship between PERP expression and the degree of infiltration of specific immune cell subsets in LUAD was evaluated using the TIMER database and GEPIA. We also performed GO enrichment analysis and KEGG enrichment analysis to reveal genes coexpressed with PERP using the Coexpedia database. Finally, we verified the expression and function of PERP in LUAD tissues and the A549 cell line by RT‒PCR, Western blot, CCK-8, IHC, and wound healing assays. The mouse model was used to study the in vivo effects of PERP.Results: According to our results, PERP expression was significantly higher in LUAD tissues and associated with the clinical characteristics of the disease. Survival was independently associated with PERP in LUAD patients. We further verified that PERP might regulate B-cell infiltration in LUAD to affect the prognosis of LUAD. To identify PERP-related signalling pathways in LUAD, we performed a genome-aggregation analysis (GSEA) between low and high PERP expression datasets. LUAD cells express higher levels of PERP than paracarcinoma cells, and PERP inhibits the proliferation and metastasis of A549 cells through apoptosis.Conclusion: PERP may affect the prognosis of lung adenocarcinoma by inhibiting apoptosis and is associated with immune cell infiltration.Keywords: PERP, lung adenocarcinoma, apoptosis, prognosis

Keywords

• perp
• lung adenocarcinoma
• apoptosis
• prognosis