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.

中文翻译：

---

非小细胞肺癌AT II相关基因的分子特征及预后价值综合分析


II 型肺泡 (AT II) 是远端肺上皮的关键结构，对于维持正常的肺稳态至关重要。 AT II 细胞的去分化与肺肿瘤进展显着相关。然而，AT II相关基因对肺癌的潜在分子机制和临床意义尚未完全阐明。在本研究中，我们综合分析了Nonsmall中8个AT II相关基因（AQP4、SFTPB、SFTPC、SFTPD、CLDN18、FOXA2、NKX2-1和PGC）的基因表达、预后价值、遗传改变和免疫细胞浸润。细胞肺癌（NSCLC）。结果显示，8个基因的表达在癌症组织中显着降低，并且与临床癌症分期明显相关。对这八个基因的生存分析显示，CLDN18、FOXA2、NKX2-1、PGC、SFTPB、SFTPC 和 SFTPD 的低表达与无进展生存期 (FP) 降低显着相关，并且 CLDN18、FOXA2 和 SFTPD 低表达mRNA 表达导致进展后生存期 (PPS) 较短。同时，8 个 AT II 相关基因的改变覆盖了 1053 个 NSCLC 样本中的 273 个样本（26%）。此外，8个基因的表达水平与多种免疫细胞的浸润显着相关，包括六种类型的CD4+T细胞、巨噬细胞、中性粒细胞、B细胞、CD8+T细胞和树突状细胞。总之，本研究提供了8个AT II相关基因作为NSCLC临床生物标志物和治疗靶点的价值线索，并可能为辅助新免疫疗法的设计提供一些新的启发。