Specific effects of hypoxia-immune core gene on lung adenocarcinoma.

BACKGROUND

The changes in tumor microenvironment (TME) are closely related to the regulation of immunity and hypoxia. This study aimed to investigate the specific effects of on the prognosis, immunity, and hypoxia of lung adenocarcinoma (LUAD).

METHODS

The core gene related to immunity and hypoxia was obtained from a variety of databases, including Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Tumor Immune Estimation Resource (TIMER), the Search Tool for the Retrieval of Interacting Genes (STRING), HALLMARK gene set, and various analysis methods (differences and single factor Cox analysis). The relationship between the expression level of , survival prognosis, immune invasion, and hypoxia regulation was analyzed.

RESULTS

was associated with poor patient prognosis and was strongly associated with immune and hypoxic-related signal pathways. We also found that knocking down the expression of can affect the proliferation, glycolysis, migration, invasion, and anti-apoptotic ability of tumor cells. The changes of apoptosis-related proteins (BCL2, BAX, and Caspase-3), cell cycle protein E1, D1 (cyclin D1, cyclin E1), matrix metalloproteinase 2 and 9 (MMP2, MMP9), and P-Phosphatidylinositol 3-kinase and protein kinase B (P-PI3K and P-AKT) in the knockdown group, were verified by Western blot (WB). We also found that interfering with the expression of can reduce the expression of programmed cell death ligand 1 (PDL1) in LUAD cells. Through the induction of tumor cells by cobalt chloride (CoCL2), we established a hypoxic microenvironment, and found that interfering with can significantly reduce the expression of hypoxia-inducible factor 1A (), downstream molecular vascular endothelial growth factor A (VEGFA), and lactate dehydrogenase A (LDHA).

CONCLUSIONS

The expression of is highly correlated with immunity, hypoxia, poor prognosis, and tumor cell development. Therefore, the study of can provide more ideas on comprehensive treatment and prognosis management of LUAD.