Abstract
BackgroundAs a critical organelle for protein and lipid synthesis, the dysfunction of endoplasmic reticulum has a significant impact on multiple biological processes of cells. Thus, in this study, we constructed an ER stress-related risk signature to investigate the functional roles of ER stress in gliomas.MethodsA total of 626 samples from TCGA RNA-seq dataset (training cohort) and 310 samples from CGGA RNA-seq dataset (validation cohort) were enrolled in this study. Clinical information and genomic profiles were also obtained. The ER stress signature was developed by the LASSO regression model. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan-Meier and ROC Curve analyses. Bioinformatics analysis and experiment in vitro were performed to explore the biological implication of this signature.ResultsWe found that the ER stress-related signature was tightly associated with major clinicopathological features and genomic alterations of gliomas. Kaplan-Meier curve and Cox regression analysis indicated that ER stress activation was an independent prognostic factor for patients with glioma. Besides, we also constructed an individualized prognosis prediction model through Nomogram and ROC Curve analysis. Bioinformatics analysis suggested that ER stress activation also promoted the malignant progression of glioma and participated in the regulation of tumor immune microenvironment, especially the infiltration of macrophages in M2 phase. These results were further validated in IHC analysis and cell biology experiments.ConclusionThe ER stress activation had a high prognostic value and could serve as a promising target for developing individualized treatment of glioma.
Highlights
Glioma is the most common and aggressive tumor in central nervous system (Wen and Kesari, 2008; Ricard et al, 2012; Jiang et al, 2016)
In order to explore the association of endoplasmic reticulum (ER) stress status with the clinical characteristics and prognosis of patients with diffuse gliomas, consensus clustering analyses were performed with ER stress related genes in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) RNA sequencing datasets
Since the ER stress-related signature was tightly associated with malignant progression of glioma, we further investigate the prognostic value of the risk signature
Summary
Glioma is the most common and aggressive tumor in central nervous system (Wen and Kesari, 2008; Ricard et al, 2012; Jiang et al, 2016). Cancer cells could acquire drug resistance and survive chemotherapies through ER stress mediated dormancy and immunosuppression (Hamanaka et al, 2005; Lee et al, 2014; Cubillos-Ruiz et al, 2017). These researches indicated that ER stress might be a valuable target for the treatment of malignant tumors. As a critical organelle for protein and lipid synthesis, the dysfunction of endoplasmic reticulum has a significant impact on multiple biological processes of cells. In this study, we constructed an ER stress-related risk signature to investigate the functional roles of ER stress in gliomas
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
