Research on Effect of CD47 on Immune Microenvironment and Immunotherapy of Lung Squamous Cell Carcinoma Based on Bioinformatics Database

OBJECTIVE To investigate the effect of gene CD47 on immune microenvironment of lung squamous cell carcinoma and predict its immune response. METHODS The differences in the expression of CD47 between lung squamous cell carcinoma tissues and normal tissues were compared through The Cancer Genome Atlas(TCGA) databases. CD47 involved immune-related pathways were analyzed by Gene Set Enrichment Analysis(GSEA). Tumor Immune Estimation Resource(TIMER) databases and TISIDB databases(http://cis.hku.hk/TISIDB/TISIDB) were employed to analyze the relationship between CD47 gene expression in lung squamous cell carcinoma and immune cells infiltration in the tumor microenvironment. And further explored the associations between CD47 and other immune-related molecules such as PD-1, PD-L1, CTLA-4, IDO-1. Using the pRRophetic and TIDE algorithms, this study predicted the correlation between the expression of CD47 gene and chemotherapy drug sensitivity as well as the response to immunotherapy. RESULTS Compared with normal tissues, CD47 was lower expressed in lung squamous cell carcinoma tissues. It was found that CD47 could activate immune-related pathways such as the inflammatory response, interferon alpha response, interferon gamma response and JAK-STAT pathway. In lung squamous cell carcinoma tissues, the expression level of CD47 was significantly positively correlated with the infiltration level of B-cells, CD8T-cells, CD4T-cells, macrophage, neutrophils and dendritic cells according to the two databases. At the same time, CD47 showed a positive correlation with other immune checkpoints such as PD-1, PD-L1, CTLA-4, IDO1. The result of chemotherapy sensitivity indicated that in lung squamous cell carcinoma tissues, IC₅₀ values of high expression CD47 group were lower than that for chemotherapy drugs such as sunitinib, dasatinib, doxorubicin and gemcitabine. However, the response rate to immunotherapy was lower in the low expression group for the immunotherapy. CONCLUSION CD47 is low expressed in lung squamous tissue, it can activate immune related pathways, and has a high response rate to immunotherapy. It can be used as a novel molecular marker for lung squamous cell carcinoma.