title: An expression based REST signature predicts patient survival and therapeutic response for glioblastoma multiforme.
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.
authors.affiliation: Department of Neurosurgery, Peking University International Hospital, Beijing, 102206, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Nutrition, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong Province, 250013, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China.
authors.forename: Wanni
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Tong
authors.affiliation: Department of Hematology, Tongji Hospital of Tongji University, Shanghai, 200065, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Peking University International Hospital, Beijing, 102206, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis*; D015996:Survival Rate; D000099229:RE1-Silencing Transcription Factor
chemical_list: D009363:Neoplasm Proteins; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor