Comprehensive Analysis of Prognostic Value and Immune Infiltration of ATⅡ-associated Genes in Non-small Cell Lung Cancer

Abstract Background: Lung cancer is one of the most commonly diagnosed cancer and the leading cause of cancer-related death in the world. ATⅡ（alveolar type II cells, ATⅡ ）are a key structure of the distal lung epithelium and have a secretory function that is essential to maintain normal lung homeostasis. ATⅡ cells dedifferentiate into a cell stem-like state, which can continuous differentiation, proliferation, repair and damage, and helps initiate and maintain tumor progression. However, the potential mechanistic value of ATⅡ-associated genes as a clinical biomarker and therapeutic target of NSCLC has not been fully elucidated.Methods: We used the Gene Expression Profile Interaction Analysis (GEPIA) and Oncomine database to explore the expression of ATⅡ-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC) in NSCLCpatients. Then we euse the Kaplan Meierplotter and the GEPIA website to evaluate the prognosis of survival impact of differential expression of these genes. Finally, we analyzed the correlation between eight ATⅡ-associated genes and infiltration of immune cells using the TIMER website.Results: The expression levels of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC were remarkably reduced in lung cancer tissues, and also observably related to clinical cancer stages. Low mRNA expression of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC were associated with short overall survival (OS) in NSCLS patients and the low expression of CLDN18, FOXA2, NKX2-1, PGC, SFTPB, SFTPC, SFTPD were significantly related to a reduced progression-free survival (FP), and low CLDN18, FOXA2 and SFTPD mRNA expression led to a short post-progression survival (PPS). Moreover, the functions of the differentially expressed eight ATⅡ-associated genes were primarily related to lung development, regulation of epithelial to mesenchymal transition, late endosome, antibacterial humoral response. Finally, the expression of AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC in LUAD and LUSC patients were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells.Conclusion: Our study provided strong evidence of the values of ATⅡ-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1 and PGC) as clinical biomarkers and therapeutic targets in NSCLC and might provide some new inspirations to assist in the design of new immunotherapies.