ERO1L Is a Novel and Potential Biomarker in Lung Adenocarcinoma and Shapes the Immune-Suppressive Tumor Microenvironment

Abstract

BackgroundThe endoplasmic reticulum oxidoreductin-1-like (ERO1L) gene encodes an endoplasmic reticulum luminal localized glycoprotein known to associated with hypoxia, however, the role of ERO1L in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in lung adenocarcinoma (LUAD).MethodsIn 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 ERO1L 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.ResultsThis study found that ERO1L was significantly overexpressed in LUAD in comparison to normal tissue. This overexpression was found to be a result of hypomethylation of the ERO1L promoter. Overexpression of ERO1L resulted in an immune-suppressive TIME via the recruitment of immune-suppressive cells including regulatory T cells (Tregs), 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 ERO1Lhigh group possessed a significantly lower response rate to immunotherapy in comparison to the ERO1Llow group. Mechanistic analysis revealed that overexpression of ERO1L was associated with the upregulation of JAK-STAT and NF-κB signaling pathways, thus affecting chemokine and cytokine patterns in the TIME.ConclusionsThis study found that overexpression of ERO1L was associated with poor prognoses in patients with LUAD. Overexpression of ERO1L 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 ERO1L as a biomarker for immunotherapy efficacy in LUAD.

PSMD13 is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma

“…This suggests that excessive immune in ltration may lead to a poor prognosis of the tumor. The relevant research is consistent with our ndings [31][32][33][34] . With the exception of this, the correlation between PSMD13 and the gene expression of some immune markers supports the view that PSMD13 may regulate the immune response in the tumor microenvironment by affecting the gene expression of immune cells.…”

Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma

“…In addition to acting as a first line of defense against various pathogens, immune cells can provide surveillance functions by recognizing and destroying latent cancer cells. Immunocompetent tumor-infiltrating cells are a unique type of immune cells [ 38 ] that infiltrate the tumor microenvironment by detecting tumor antigens and releasing proinflammatory and immune molecules that regulate immune function. In addition, although cancer immunotherapy has been shown to improve survival in a variety of cancers, remission rates in patients with PAAD remain low [ 39 ].…”

Autophagy-Related Gene Signature Highlights Metabolic and Immunogenic Status of Malignant Cells in Non-Small Cell Lung Cancer Adenocarcinoma

“…ERO1L has already been demonstrated to play a critical role in NSCLC, promoting cancer development by modulating cell cycle-related molecules [ 27 ]. Moreover, recent reports also mentioned that ERO1L was implicated in anti-tumor immune response, by preventing T cell-mediated immunity and favoring myeloid suppressor cell activation [ 28 , 29 ]. The expression of ERO1L gene in malignant cells could explain, at least in part, the reason for which signature B is associated with a bad prognosis, low infiltration of immune cells and high proliferative rates.…”