Assessment of bevacizumab resistance increased by expression of BCAT1 in IDH1 wild-type glioblastoma: application of DSC perfusion MR imaging
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Hye Rim Cho1,2, Bora Hong1,2, Hyeonjin Kim1, Chul-Kee Park3, Sung-Hye Park4, Sunghyouk Park5, Seung Hong Choi1,2
1Department of Radiology, Seoul National University Hospital, Seoul, Korea
2Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, Korea
3Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea
4Department of Pathology, Seoul National University Hospital, Seoul, Korea
5College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul, Korea
Seung Hong Choi, email: email@example.com
Keywords: BCAT1, dynamic susceptibility contrast (DSC), bevacizumab, glioblastoma
Received: December 29, 2015 Accepted: September 02, 2016 Published: September 08, 2016
BCAT1 (branched-chain amino acid trasaminase1) expression is necessary for the progression of IDH1 wild-type (WT) glioblastoma multiforme (GBM), which is known to be associated with aggressive tumors. The purpose of our study is to investigate the bevacizumab resistance increased by the expression of BCAT1 in IDH1 WT GBM in a rat model, which was evaluated using DSC perfusion MRI. BCAT1 sh#1 inhibits cell proliferation and limits cell migration potential in vitro. In vivo MRI showed that the increase in both tumor volume and nCBV after bevacizumab treatment in IDH1 WT tumors was significantly higher compared with BCAT1 sh#1tumors. In a histological analysis, more micro-vessel reformation by bevacizumab resistance was observed in IDH1 WT tumors than BCAT1 sh#1 tumors. These findings indicate that BCAT1 expression in IDH1 WT GBM increases resistance to bevacizumab treatment, which could be assessed by DSC perfusion MRI, and that nCBV can be a surrogate imaging biomarker for the prediction of antiangiogenic treatment in GBM.
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