A Novel Defined Endoplasmic Reticulum Stress-Related lncRNA Signature for Prognosis Prediction and Immune Therapy in Glioma

Yinfei Zheng; Xiaoyu Yue; Cheng Fang; Zhuang Jia; Yuxiang Chen; Han Xie; Jiajia Zhao; Zhihao Yang; Lianxin Li; Zhigang Chen; Erbao Bian; Bing Zhao

doi:10.3389/fonc.2022.930923

A Novel Defined Endoplasmic Reticulum Stress-Related lncRNA Signature for Prognosis Prediction and Immune Therapy in Glioma

Front Oncol. 2022 Jun 30:12:930923. doi: 10.3389/fonc.2022.930923. eCollection 2022.

Authors

Yinfei Zheng^{1

2}, Xiaoyu Yue^{1

2}, Cheng Fang^{1

2}, Zhuang Jia^{1

2}, Yuxiang Chen^{1

2}, Han Xie^{1

2}, Jiajia Zhao^{1

2}, Zhihao Yang^{1

2}, Lianxin Li^{1

2}, Zhigang Chen^{1

2}, Erbao Bian^{1

2}, Bing Zhao^{1

2}

Affiliations

¹ Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
² Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei, China.

Abstract

Gliomas are a group of the most aggressive primary central nervous system tumors with limited treatment options. The abnormal expression of long non-coding RNA (lncRNA) is related to the prognosis of glioma. However, the role of endoplasmic reticulum (ER) stress-associated lncRNAs in glioma prognosis has not been reported. In this paper, we obtained ER stress-related lncRNAs by co-expression analysis, and then a risk signature composed of 6 ER stress-related lncRNAs was constructed using Cox regression analysis. Glioma samples in The Cancer Genome Atlas (TCGA) were separated into high- and low-risk groups based on the median risk score. Compared with the low-risk group, patients in the high-risk group had shorter survival times. Additionally, we verified the predictive ability of these candidate lncRNAs in the testing set. Three glioma patient subgroups (cluster 1/2/3) were identified by consensus clustering. We further analysed the abundance of immune-infiltrating cells and the expression levels of immune checkpoint molecules in both three subgroups and two risk groups, respectively. Immunotherapy and anticancer drug response prediction showed that ER stress-related lncRNA risk signature positively correlates with responding to immune checkpoints and chemosensitivity. Functional analysis showed that these gene sets are enriched in the malignant process of tumors. Finally, LINC00519 was chosen for functional experiments. The silence of LINC00519 restrained the migration and invasion of glioma cells. Hence, those results indicated that ER stress-related lncRNA risk signature could be a potential treatment target and a prognosis biomarker for glioma patients.

Keywords: endoplasmic reticulum stress; glioma; immune; lncRNA; prognosis; risk signature.