Zou Hecun, Wu Lan-Xiang, Yang Yonglong, Li Shuang, Mei Ying, Liu Yong-Bin, Zhang Lihua, Cheng Yu, Zhou Hong-Hao
Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, China.
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China.
Oncotarget. 2017 Aug 12;8(45):78767-78780. doi: 10.18632/oncotarget.20226. eCollection 2017 Oct 3.
Diffuse gliomas are well known malignant brain tumors. Long non-coding RNAs (lncRNAs), a type of RNA transcript with more than 200 nucleotides, involve in tumorigenesis and development of various cancers. This study focused on identifying differentially expressed lncRNAs in gliomas based on gene expression profiling, and chose certain lncRNAs PVT1, CYTOR, HAR1A and MIAT, which changed with significant differences. Further analysis of TCGA and GEO data revealed that the expressions of PVT1 and CYTOR were up-regulated, while HAR1A and MIAT expressions were down-regulated in gliomas. Their expression patterns were validated in an independent cohort containing 98 glioma specimens and 12 non-tumor tissue controls. High expression of PVT1 and CYTOR as well as low HAR1A and MIAT expression were associated with high Ki-67 level and more mutation. Kaplan-Meier survival curve and Cox regression analyses showed that glioma patients with high PVT1 expression or low HAR1A expression had poor survival outcome, aberrantly expressed PVT1 and HAR1A could be the independent prognosis biomarkers for glioma patients. Moreover, down-regulation of PVT1 and up-regulation of HAR1A contributed to improve the survival of patients who received chemotherapy and radiotherapy. These results implied that these four lncRNAs might play important role in diffuse gliomas progression, particularly, PVT1 and HAR1A could be explored as promising biomarkers for diagnosis, prognosis and target therapy of diffuse gliomas.
弥漫性胶质瘤是众所周知的恶性脑肿瘤。长链非编码RNA（lncRNAs）是一类长度超过200个核苷酸的RNA转录本，参与多种癌症的发生和发展。本研究基于基因表达谱鉴定胶质瘤中差异表达的lncRNAs，并选取了差异显著的某些lncRNAs，即PVT1、CYTOR、HAR1A和MIAT。对TCGA和GEO数据的进一步分析显示，胶质瘤中PVT1和CYTOR的表达上调，而HAR1A和MIAT的表达下调。在一个包含98例胶质瘤标本和12例非肿瘤组织对照的独立队列中验证了它们的表达模式。PVT1和CYTOR的高表达以及HAR1A和MIAT的低表达与高Ki-67水平和更多突变相关。Kaplan-Meier生存曲线和Cox回归分析表明，PVT1高表达或HAR1A低表达的胶质瘤患者生存结局较差，异常表达的PVT1和HAR1A可能是胶质瘤患者的独立预后生物标志物。此外，PVT1的下调和HAR1A的上调有助于改善接受化疗和放疗患者的生存。这些结果表明，这四种lncRNAs可能在弥漫性胶质瘤进展中发挥重要作用，特别是PVT1和HAR1A有望作为弥漫性胶质瘤诊断、预后和靶向治疗的生物标志物进行探索。
