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.

PARP‐1 regulates DNA repair factor availability

“…Additionally, these observations align with studies demonstrating that PARP‐1 and PAR are elevated in PCa compared to benign prostatic hyperplasia in a Chinese cohort (Wu et al , ) and that PARP‐1 protein is elevated in cases of primary PCa as compared to normal controls (Salemi et al , ). In other tumor types, elevated PARP‐1 mRNA is associated with poor prognosis in gliomas (Li et al , ), PARP‐1 mRNA is elevated in colon carcinoma when compared to adenoma (Dziaman et al , ), PARP‐1 gene expression is associated with lymph node spread of malignant pleural mesothelioma (Walter et al , ), and PARP‐1 mRNA and protein are elevated in endometrial adenocarcinoma (Bi et al , ). Both PARP‐1 mRNA and protein are highly expressed in small cell lung cancer (Byers et al , ), but PARP‐1 protein has been shown to associate with longer PFS in limited‐stage small cell lung cancer (Kim et al , ).…”

PARP and PARG inhibitors in cancer treatment

“…The expression levels of PARP1 itself may also determine PARP inhibitor response. PARP1 expression is increased in different cancer types, particularly at advanced stages (Ossovskaya et al 2010;Domagala et al 2011;Mascolo et al 2012;Bi et al 2013;Bieche et al 2013;Gan et al 2013;Salemi et al 2013;Dziaman et al 2014;Park et al 2015;Zhai et al 2015;Li et al 2016;Hou et al 2018), and in some cases correlates positively with the cytotoxic effects of PARP inhibition (Byers et al 2012;Kukolj et al 2017).…”

31 gene expression‑based signatures serve as indicators of prognosis for patients with glioma

“…Genetic alterations of glioma have been frequently reported previously (8,9,29,30). Genetic heterogeneity across individuals has also been reported (31).…”