LncRNA profile study reveals four-lncRNA signature associated with the prognosis of patients with anaplastic gliomas

// Wen Wang 1, 2, 3, 7 , Fan Yang 1, 3, 7 , Lu Zhang 5 , Jing Chen 3, 4, 7 , Zheng Zhao 3, 4, 7 , Haoyuan Wang 6, 7 , Fan Wu 3, 4, 7 , Tingyu Liang 1, 3, 7 , Xiaoyan Yan 3, 4, 7 , Jiye Li 4 , Qing Lan 2 , Jiangfei Wang 1, 7 , Jizong Zhao 1, 2, 8 1 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2 Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China 3 Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China 4 Beijing Neurosurgical Institute, Capital Medical University, Beijing, China 5 Department of Ophthalmology, School of Medicine, Shandong University, Jinan, China 6 Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China 7 Chinese Glioma Cooperative Group (CGCG), Beijing, China 8 China National Clinical Research Center for Neurological Diseases, Beijing, China Correspondence to: Jizong Zhao, email: zhaojz205@163.com Keywords: signature, prognosis, anaplastic glioma, lncRNA, RNA microarray Received: March 11, 2016 Accepted: September 25, 2016 Published: October 13, 2016 ABSTRACT Anaplastic glioma is Grade III and the median overall survival is about 37.6 months. However, there are still other factors that affect the prognosis for anaplastic glioma patients due to variable overall survival. So we screened four-lncRNA signature (AGAP2-AS1, TPT1-AS1, LINC01198 and MIR155HG) from the lncRNA expression profile from the GSE16011, CGGA and REMBRANDT datasets. The patients in low risk group had longer overall survival than high risk group (median OS 2208.25 vs. 591.30 days; P < 0.0001). Moreover, patients in the low risk group showed similar overall survival to Grade II patients (P = 0.1669), while the high risk group showed significant different to Grade IV (P = 0.0005) with similar trend. So based on the four-lncRNA, the anaplastic gliomas could be divided into grade II-like and grade IV-like groups. On the multivariate analysis, it showed the signature was an independent prognostic factor (P = 0.000). The expression of four lncRNAs in different grades showed that AGAP2-AS1, LINC01198 and MIR155HG were increased with tumor grade, while TPT1-AS1 was decreased. Knockdown of AGAP2-AS1 can inhibit the cell proliferation, migration and invasion, while increase the apoptosis cell rates in vitro. In conclusion, our results showed that the four-lncRNA signature has prognostic value for anaplastic glioma. Moreover, clinicians should conduct corresponding therapies to achieve best treatment with less side effects for two groups patients.