Is a Novel and Potential Biomarker in Lung Adenocarcinoma and Shapes the Immune-Suppressive Tumor Microenvironment.

BACKGROUND

The endoplasmic reticulum oxidoreductin-1-like () gene encodes an endoplasmic reticulum luminal localized glycoprotein known to associated with hypoxia, however, the role of in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in lung adenocarcinoma (LUAD).

METHODS

In this study, raw datasets (including RNA-seq, methylation, sgRNA-seq, phenotype, and survival data) were obtained from public databases. This data was analyzed and used to explore the biological landscape of in immune infiltration. Expression data was used to characterize samples. Using gene signatures and cell quantification, stromal and immune infiltration was determined. These findings were used to predict sensitivity to immunotherapy.

RESULTS

This study found that was significantly overexpressed in LUAD in comparison to normal tissue. This overexpression was found to be a result of hypomethylation of the promoter. Overexpression of resulted in an immune-suppressive TIME the recruitment of immune-suppressive cells including regulatory T cells (T), cancer associated fibroblasts, M2-type macrophages, and myeloid-derived suppressor cells. Using the Tumor Immune Dysfunction and Exclusion (TIDE) framework, it was identified that patients in the group possessed a significantly lower response rate to immunotherapy in comparison to the group. Mechanistic analysis revealed that overexpression of was associated with the upregulation of JAK-STAT and NF-κB signaling pathways, thus affecting chemokine and cytokine patterns in the TIME.

CONCLUSIONS

This study found that overexpression of was associated with poor prognoses in patients with LUAD. Overexpression of was indicative of a hypoxia-induced immune-suppressive TIME, which was shown to confer resistance to immunotherapy in patients with LUAD. Further studies are required to assess the potential role of as a biomarker for immunotherapy efficacy in LUAD.