Research Paper Volume 12, Issue 10 pp 9188—9204
A three-lncRNA signature predicts clinical outcomes in low-grade glioma patients after radiotherapy
- 1 Department of Radiation Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China
- 2 Department of Radiation Oncology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, China
- 3 Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 4 Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- 5 Division of Neurocritical Care, Huashan Hospital, Fudan University, Shanghai, China
- 6 Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Shanghai, China
Received: November 21, 2019 Accepted: April 17, 2020 Published: May 26, 2020
https://doi.org/10.18632/aging.103189How to Cite
Copyright © 2020 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Although radiation therapy (RT) plays a critical role in the treatment of low-grade glioma (LGG), many patients suffer from adverse effects without experiencing survival benefits. In various carcinomas, long non-coding RNAs (lncRNAs) contribute to pathogenic processes, including tumorigenesis, metastasis, chemoresistance, and radioresistance. Currently, the role of lncRNAs in the radiosensitivity of LGG is largely unknown. Here, we downloaded clinical data for 167 LGG patients from The Cancer Genome Atlas database and divided them between radiosensitive and radioresistant groups based on their clinical outcomes after receiving radiotherapy. We identified 37 lncRNAs that were differentially expressed (DElncRNAs) between the groups. Functional enrichment analysis revealed that their potential target mRNAs were mainly enriched in the PI3K-Akt and MAPK signaling pathways and in DNA damage response. Kaplan-Meier survival analysis revealed that increased expression of six lncRNAs was significantly associated with radiosensitivity. We then developed a risk signature based on three of the DElncRNAs that served as an independent biomarker for predicting LGG patient outcomes after radiotherapy. In vitro experiments further validated the biological function of these lncRNAs on low-grade glioma radiation response.
Abbreviations
RT: radiation therapy; LGG: low-grade glioma; lncRNAs: long non-coding RNAs; DElncRNAs: differentially expressed lncRNAs; WGCNA: weighted correlation network analysis; OS: overall survival; PFS: progression-free survival; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; EMT: epithelial–mesenchymal transition; PD-L1: programmed death ligand-1; TCGA: The Cancer Genome Atlas.