Survival kinase genes present prognostic significance in glioblastoma

Abstract

// Robin T. Varghese 1 , Yanping Liang 1 , Ting Guan 2 , Christopher T. Franck 1, 2 , Deborah F. Kelly 1, 3, 4, 6 , Zhi Sheng 1, 4, 5, 6 1 Virginia Tech Carilion Research Institute, Roanoke, VA 24016, USA 2 Laboratory for Interdisciplinary Statistical Analysis, Department of Statistics, Virginia Tech, Blacksburg, VA 24061, USA 3 Department of Biological Sciences, College of Sciences at Virginia Tech, Blacksburg, VA 24061, USA 4 Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA 5 Department of Biological Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA 6 Faculty of Health Science, Virginia Tech, Blacksburg, VA 24061, USA Correspondence to: Zhi Sheng, e-mail: zhisheng@vtc.vt.edu Keywords: survival kinase genes, glioblastoma, tumor recurrence, prognosis, PIK3CB Received: December 22, 2015      Accepted: February 14, 2016      Published: March 04, 2016 ABSTRACT Cancer biomarkers with a strong predictive power for diagnosis/prognosis and a potential to be therapeutic targets have not yet been fully established. Here we employed a loss-of-function screen in glioblastoma (GBM), an infiltrative brain tumor with a dismal prognosis, and identified 20 survival kinase genes (SKGs). Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that the expression of CDCP1, CDKL5, CSNK1E, IRAK3, LATS2, PRKAA1, STK3, TBRG4, and ULK4 stratified GBM prognosis with or without temozolomide (TMZ) treatment as a covariate. For the first time, we found that GBM patients with a high level of NEK9 and PIK3CB had a greater chance of having recurrent tumors. The expression of CDCP1, IGF2R, IRAK3, LATS2, PIK3CB, ULK4, or VRK1 in primary GBM tumors was associated with recurrence-related prognosis. Notably, the level of PIK3CB in recurrent tumors was much higher than that in newly diagnosed ones. Congruent with these results, genes in the PI3K/AKT pathway showed a significantly strong correlation with recurrence rate, further highlighting the pivotal role of PIK3CB in the disease progression. Importantly, 17 SKGs together presented a novel GBM prognostic signature. SKGs identified herein are associated with recurrence rate and present prognostic significance in GBM, thereby becoming attractive therapeutic targets.