Integrative analysis of genomic alteration, immune cells infiltration and prognosis of lung squamous cell carcinoma (LUSC) to identify smoking-related biomarkers.

Lung squamous cell carcinoma (LUSC) is the most common histologic type of smoking-related non-small cell lung cancer (NSCLC). However, there are no identified potential biomarkers for smoking-related LUSC diagnosis and prognosis. Especially, the characteristics of genetic alteration and tumor microenvironment induced by cigarette smoking remain unknown. Here, we performed integrative analysis of 463 LUSC with smoking history information from The Cancer Genome Atlas (TCGA). Non-smokers had the best prognosis, and current reformed smokers had better overall survival (OS) than current smokers in all and stage I-II cohort. Then, pathway enrichment analysis might suggest that smoking may play a role in regulating tumor metabolism and invasion and metastasis via those pathways. We constructed an eight-gene signature and identified WNT7A, Solute carrier-7A5 (SLC7A5) and Brain‑type glycogen phosphorylase (PYGB), which may be served as biomarkers related to the smoking. Notably, the single copy deletion of WNT7A and SLC17A5 and the low-level amplification of PYGB may be related to the epigenetic mechanism of smoking on tumorigenesis. We also estimated the relative proportion of 24 immune cell subtypes within tumor microenvironment in different smoking status. Interestingly, we found NK cells activated, NK cells resting and endothelial cells might play an important role in immunologic dysfunction and harmful tumor microenvironment induced by cigarette smoking. Our research has identified potential biomarkers for smoking-related LUSC diagnosis and prognosis, which would help to further understand the pathogenesis of LUSC.