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三长链非编码 RNA 标志物预测放疗后低级别胶质瘤患者的临床结局。

A three-lncRNA signature predicts clinical outcomes in low-grade glioma patients after radiotherapy.

机构信息

Department of Radiation Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou, China.

Department of Radiation Oncology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, China.

出版信息

Aging (Albany NY). 2020 May 26;12(10):9188-9204. doi: 10.18632/aging.103189.

DOI:10.18632/aging.103189
PMID:32453707
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7288909/
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.

摘要

虽然放射治疗（RT）在低级别胶质瘤（LGG）的治疗中起着关键作用，但许多患者在没有生存获益的情况下遭受不良反应。在各种癌中，长链非编码 RNA（lncRNA）有助于包括肿瘤发生、转移、化疗耐药和放疗耐药在内的发病过程。目前，lncRNA 在 LGG 放疗敏感性中的作用在很大程度上尚不清楚。在这里，我们从癌症基因组图谱数据库中下载了 167 名 LGG 患者的临床数据，并根据他们接受放疗后的临床结果将其分为放疗敏感组和放疗抵抗组。我们鉴定出 37 个在两组之间差异表达的 lncRNA（DElncRNA）。功能富集分析显示，其潜在靶 mRNA 主要富集在 PI3K-Akt 和 MAPK 信号通路以及 DNA 损伤反应中。Kaplan-Meier 生存分析显示，六种 lncRNA 的高表达与放疗敏感性显著相关。然后，我们基于三个作为预测 LGG 患者放疗后预后的独立生物标志物的 DElncRNA 开发了一个风险签名。体外实验进一步验证了这些 lncRNA 在低级别胶质瘤放射反应中的生物学功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c6/7288909/b2229093e190/aging-12-103189-g008.jpg
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