title: Expression of ADP-ribosyltransferase 1 Is Associated with Poor Prognosis of Glioma Patients.
abstract: Glioma has a poor prognosis due to its rapid overgrowth, diffuse invasion, and chemotherapy resistance. The improvements in clinical outcome are still limited and the identification of novel biomarkers involved in the progression of gliomas is still under critical demands. Amino acid ADP-ribosyltransferase 1 (ART1) is an enzyme that catalyzes the mono-ADP-ribosylation, a reversible post-translational modification. For example, the mono-ADP-ribosylation of transcription factors can affect their binding to target gene promoters. However, the functional significance of ART1 in glioma has not been reported. We collected 107 glioma cases from Qianfoshan Hospital and Yidu Central Hospital of Weifang between April 2008 and September 2015 to analyze the prognosis value of ART1 in gliomas. RT-qPCR analysis showed that the expression level of ART1 mRNA in glioma tissues was 4-fold higher than that in normal brain tissues. According to the immunohistochemical staining results, 44 patients (41.1%) were categorized as ART1 positive (≥ 20% of stained glioma cells), while the other 63 patients (58.9%) categorized as ART1 negative (< 20% of stained glioma cells). Moreover, the mean percentage of ART1-positive cells was 43.7%, 53.6% and 64.2% in WHO grade II, III and IV specimens, respectively. Through univariate and multivariate analyses, we identified ART1 as an independent prognostic factor. We also found that ART1 overexpression in U251 glioblastoma cells could significantly decrease the susceptibility to vincristine, one of tubulin-targeted drugs, which is widely used in clinical treatment for glioma. Taken together, we propose that up-regulation of ART1 expression is associated with the aggressiveness of glioma.
authors.affiliation: Department of Neurology, Yidu Central Hospital of Weifang.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Xinling
authors.initials: X
authors.lastname: Yan
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yang
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D014404:Tubulin / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology
chemical_list: D058851:GPI-Linked Proteins; D014404:Tubulin; D014750:Vincristine; D036002:ADP Ribose Transferases; C449301:ART1 protein, human