Identification of prognostic hypoxia-related genes signature on the tumor microenvironment in esophageal cancer

Abstract

Background: Hypoxia is a crucial factor in the development of esophageal cancer. The relationship between hypoxia and immune status in the esophageal cancer microenvironment is becoming increasingly important in clinical practice. This study aims to clarify and investigate the possible connection between immunotherapy and hypoxia in esophageal cancer. Methods: The Cancer Genome Atlas databases are used to find two types of esophageal cancer cases. Cox regressions analyses are used to screen genes for hypoxia-related traits. After that, the genetic signature is validated by survival analysis and the construction of ROC curves. GSEA is used to compare differences in enrichment in the two groups and is followed by the CIBERSORT tool to investigate a potentially relevant correlation between immune cells and gene signatures. Results: We found that the esophageal adenocarcinoma hypoxia model contains 3 genes (PGK1, PGM1, SLC2A3), and the esophageal squamous cell carcinoma hypoxia model contains 2 genes (EGFR, ATF3). The findings demonstrated that the survival rate of patients in the high-risk group is lower than in the lower-risk group. Furthermore, we find that three kinds of immune cells (memory activated CD4+ T cells, activated mast cells, and M2 macrophages) have a marked infiltration in the tissues of patients in the high-risk group. Moreover, we find that PD-L1 and CD244 are highly expressed in high-risk groups. Conclusions: Our data demonstrate that oxygen deprivation is correlated with prognosis and the incidence of immune cell infiltration in patients with both types of esophageal cancer, which provides an immunological perspective for the development of personalized therapy.

Keywords

• hypoxia
• esophageal cancer
• tumor microenvironment
• immune cell infiltration
• gene set enrichment analysis