Identification of an endoplasmic reticulum stress-related signature associated with clinical prognosis and immune therapy in glioma

Abstract

Abstract Background Glioma is the most common brain tumor in adults and is characterized by a short survival time and high resistance to chemotherapy. It is imperative to determine the prognosis and therapy-related targets for glioma. Endoplasmic reticulum stress (ERS), as an adaptive protective mechanism, indicates the unfolded protein response (UPR) to determine cell survival and affects chemotherapy sensitivity, which is related to the prognosis of glioma. Methods Our research used the TCGA database as the training group and the CGGA database as the testing group. Lasso regression and Cox analysis were performed to construct an ERS signature-based risk score model in glioma. Three methods (time-dependent receiver operating characteristic analysis and multivariate and univariate Cox regression analysis) were applied to assess the independent prognostic effect of texture parameters. Consensus clustering was used to classify the two clusters. In addition, functional and immune analyses were performed to assess the malignant process and immune microenvironment. Immunotherapy and anticancer drug response prediction were adopted to evaluate immune checkpoint and chemotherapy sensitivity. Results The results revealed that the 7-gene signature strongly predicts glioma prognosis. The two clusters have markedly distinct molecular and prognostic features. The validation group result revealed that the signature has exceptional repeatability and certainty. Functional analysis showed that the ERS-related gene signature was closely associated with the malignant process and prognosis of tumors. Immune analysis indicated that the ERS-related gene signature is strongly related to immune infiltration. Immunotherapy and anticancer drug response prediction indicated that the ERS-related gene signature is positively correlated with immune checkpoint and chemotherapy sensitivity. Conclusions Collectively, the ERS-related risk model can provide a novel signature to predict glioma prognosis and treatment.

Keywords

• Glioma
• Endoplasmic reticulum stress
• Gene signature
• Prognosis
• Function
• Immune therapy