Comprehensive Analysis of the Molecular Characteristics and Prognosis value of AT II-associated Genes in Non-small Cell Lung Cancer

Abstract

Alveolar type II (AT II) is a key structure of the distal lung epithelium and essential to maintain normal lung homeostasis. Dedifferentiation of AT II cells is significantly correlated with lung tumor progression. However, the potential molecular mechanism and clinical significance of AT II-associated genes for lung cancer has not yet been fully elucidated. In this study, we comprehensively analyzed the gene expression, prognosis value, genetic alteration, and immune cell infiltration of eight AT II-associated genes (AQP4, SFTPB, SFTPC, SFTPD, CLDN18, FOXA2, NKX2-1, and PGC) in Nonsmall Cell Lung Cancer (NSCLC). The results have shown that the expression of eight genes were remarkably reduced in cancer tissues and observably relating to clinical cancer stages. Survival analysis of the eight genes revealed that low-expression of CLDN18, FOXA2, NKX2-1, PGC, SFTPB, SFTPC, and SFTPD were significantly related to a reduced progression-free survival (FP), and low CLDN18, FOXA2, and SFTPD mRNA expression led to a short postprogression survival (PPS). Meanwhile, the alteration of 8 AT II-associated genes covered 273 out of 1053 NSCLC samples (26%). Additionally, the expression level of eight genes 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. In summary, this study provided clues of the values of eight AT II-associated genes as clinical biomarkers and therapeutic targets in NSCLC and might provide some new inspirations to assist the design of new immunotherapies.