| Title | An expression based REST signature predicts patient survival and therapeutic response for glioblastoma multiforme |
| Authors | Liang, Jianfeng Meng, Qinghua Zhao, Wanni Tong, Pan Li, Ping Zhao, Yuanli Zhao, Xiaodong Li, Hua |
| Affiliation | Peking Univ, Int Hosp, Dept Neurosurg, Beijing 102206, Peoples R China. Shandong Univ, Jinan Cent Hosp, Dept Nutr, Jinan 250013, Shandong, Peoples R China. Peking Univ, China Japan Friendship Sch Clin Med, Beijing 100029, Peoples R China. Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. Tongji Univ, Tongji Hosp, Dept Hematol, Shanghai 200065, Peoples R China. Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing 100050, Peoples R China. Shanghai Jiao Tong Univ, Sch Biomed Engn, BioID Ctr, Shanghai 200240, Peoples R China. |
| Keywords | CELL LUNG-CANCER DRUG-SENSITIVITY TUMOR-SUPPRESSOR STEM-CELLS NEURONAL GENES AKT PATHWAY TRANSCRIPTION REPRESSOR GLIOMAS GROWTH |
| Issue Date | 2016 |
| Publisher | SCIENTIFIC REPORTS |
| Citation | SCIENTIFIC REPORTS.2016,6. |
| Abstract | Proper regulation of neuronal gene expression is crucial for the development and differentiation of the central nervous system. The transcriptional repressor REST (repressor element-1 silencing transcription factor) is a key regulator in differentiation of pluripotent stem cells to neuronal progenitors and mature neurons. Dysregulated REST activity has been implicated in various diseases, among which the most deadly is glioblastoma multiforme (GBM). Here we have developed an expression-based REST signature (EXPREST), a device providing quantitative measurements of REST activity for GBM tumors. EXPREST robustly quantifies REST activity (REST score) using gene expression profiles in absence of clinic-pathologic assessments of REST. Molecular characterization of REST activity identified global alterations at the DNA, RNA, protein and microRNA levels, suggesting a widespread role of REST in GBM tumorigenesis. Although originally aimed to capture REST activity, REST score was found to be a prognostic factor for overall survival. Further, cell lines with enhanced REST activity was found to be more sensitive to IGF1R, VEGFR and ABL inhibitors. In contrast, cell lines with low REST score were more sensitive to cytotoxic drugs including Mitomycin, Camptothecin and Cisplatin. Together, our work suggests that therapeutic targeting of REST provides a promising opportunity for GBM treatment. |
| URI | http://hdl.handle.net/20.500.11897/492649 |
| ISSN | 2045-2322 |
| DOI | 10.1038/srep34556 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 国际医院 中日友好医院 |
