PD-1 and PD-L1 Related Comprehensive Analysis of Lung Squamous Cell Carcinoma

Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell cancer associated with poor clinical prognosis and lacks targeted agents. PD-1 and PD-L1 play a critical role in cancer immune. However, genomic alterations associated with PD-1 and PD-L1 expression in LUSC have not been comprehensively characterized. To characterize genomic landscape, we integrally analyzed related genomic and clinical prognostic value associated with PD-1 and PD-L1 in Cancer Genome Atlas (TCGA) and GEO data. Here, we showed that PD-1 and PD-L1 expression were found to demonstrate the existence of heterogeneity in tumor samples. The degrees of PD-1 and PD-L1 expression did not show prognostic significance in patients with LUSC in TCGA. Higher tumor mutation burden (TMB) showed significantly increased expression of PD-1. NFE2L2 mutations led to higher PD-L1 expression in LUSC. The expression of PD-1 and PD-L1 were correlated with tumor microenvironment cells and immune-related molecules such as CTLA4, ICOS, FOXP3, HAVCR2, CD3G, CD8A, LAG3, and PDCD1LG2. The over-expression of PD-1 and PD-L led to genomic alterations of cell adhesion molecules cams; natural killer cell mediated cytotoxicity, antigen processing and presentation, and toll-like receptor signaling pathway. Moreover, survival analysis of PD-1 related module genes shows that ITIH3, EDEM1, EPS15, SETDB2, EHD1, and ANK26 are potent predictors of prognosis in patients with LUSC. Our results indicated that PD-1 and PD-L1 alterations were involved in crucial steps of tumor immune process, and present new therapeutic opportunities for manipulation of PD-1 and PD-L1 to achieve optimal immune responses in LUSC.    Funding Statement: This project was supported by National major research program on Natural Science of China (91542164). Declaration of Interests: The authors declare that they have no competing financial interests.