Exploring the relationship between hypoxia in lung adenocarcinoma and tumor microenvironment immune cell infiltration.

BACKGROUND

The hypoxic microenvironment affects the development of many types of tumors. It also triggers a series of immune response, and affects the level of immune cells infiltration. Here, the study aims to develop a gene marker based on hypoxia for prognosis evaluation in lung adenocarcinoma (LUAD), and investigate the relationship between hypoxia and immune cell infiltration in the tumor microenvironment (TME).

METHOD

Retrieving LUAD cases from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Through bioinformatics analysis, we screened out the hypoxia genes correlated with the prognosis of LUAD. A hypoxia risk score model was established by using gene expression level and expression coefficient. Using the median risk score value, we divided the patients in the two databases into high-risk and low-risk groups. The hypoxic model was then validated using survival analysis and receiver operating characteristic (ROC) curves. The CIBERSORT calculation method was employed to analyze the infiltration of immune cells. Finally, we analyzed the correlation between immune genes and hypoxia.

RESULT

Patients in the high-risk group, characterized by higher hypoxia risk scores, exhibited significantly poorer prognosis compared to those in the low-risk group. In addition, we found significant differences in the infiltration rates of these five types of immune cells (M0 macrophages, M1 macrophages, resting mast cells, activated mast cells, monocytes, resting NK cells and activated CD4 memory T cells) in both groups of tissues. After screening, the expression levels of the four immune genes (CCR7, CXCL10, CXCL11, and CCL19) were significantly associated with hypoxia risk in both groups.

CONCLUSION

We discovered that the hypoxia risk score was related to prognosis and immune cell infiltration rate of LUAD. This finding may provide new ideas for LUAD immunotherapy.