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MR 灌注成像参数与基因组生物标志物的初步放射基因组学关联,及其对胶质母细胞瘤患者总生存的预测性能。

The preliminary radiogenomics association between MR perfusion imaging parameters and genomic biomarkers, and their predictive performance of overall survival in patients with glioblastoma.

机构信息

Department of Imaging Sciences, University of Rochester Medical Center, 601 Elmwood Avenue, PO Box 648, Rochester, NY, 14642-8638, USA.

Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA.

出版信息

J Neurooncol. 2017 Dec;135(3):553-560. doi: 10.1007/s11060-017-2602-x. Epub 2017 Sep 9.

Abstract

The radiogenomics association of neovascularization is important for overall survival (OS) in glioblastoma patients and remains unclear. The purpose of this study is to assess the association between MR perfusion imaging derived parameters and genomic biomarkers of glioblastoma, and to evaluate their prognostic value. This retrospective study enrolled 41 patients with newly diagnosed glioblastoma. The mean and maximal relative cerebral blood volume (rCBV) ratio (rCBV and rCBV), derived from MR perfusion weighted imaging, of the enhancing tumor, as well as maximal rCBV ratio of peri-enhancing tumor area (rCBV) were measured. The ki-67 labeling index, mammalian target of rapamycin (mTOR) activation, epidermal growth factor receptor (EGFR) amplification, isocitrate dehydrogenase (IDH) mutation and TP53 were assessed. There was a significant correlation between rCBV and mTOR based on Pearson's correlations with Benjamini-Hochberg adjustment for controlling false discovery rate, p = 0.047. The rCBV showed significant correlation with mTOR (p = 0.0183) after adjustment of gender and EGFR status. The mean rCBV value of the patients with OS shorter than 14 months was significantly higher than patients with OS longer than 14 months, p = 0.002. The rCBV and age were the two strongest predictors of OS (hazard ratio = 1.29 and 1.063 respectively) by Cox regression analysis. This study showed that hemodynamic abnormalities of glioblastoma were associated with genomics activation status of mTOR-EGFR pathway, however, the radiogenomics associations are different in enhancing and peri-enhancing area of glioblastoma. The rCBV has better prognostic value than genomic biomarkers alone.

摘要

磁共振灌注成像衍生参数与胶质母细胞瘤基因组生物标志物的放射基因组学关联对总体生存(OS)很重要,但目前仍不清楚。本研究旨在评估磁共振灌注成像衍生参数与胶质母细胞瘤基因组生物标志物之间的关联,并评估其预后价值。本回顾性研究纳入了 41 例新诊断的胶质母细胞瘤患者。测量增强肿瘤的平均和最大相对脑血容量(rCBV)比值(rCBV 和 rCBV)、增强肿瘤区的最大相对脑血容量比值(rCBV)以及最大相对脑血容量比值(rCBV)。评估了 ki-67 标记指数、哺乳动物雷帕霉素靶蛋白(mTOR)激活、表皮生长因子受体(EGFR)扩增、异柠檬酸脱氢酶(IDH)突变和 TP53。基于 Pearson 相关性,使用 Benjamini-Hochberg 调整进行假发现率控制,rCBV 与 mTOR 之间存在显著相关性,p=0.047。在调整性别和 EGFR 状态后,rCBV 与 mTOR 呈显著相关性,p=0.0183。OS 短于 14 个月的患者的平均 rCBV 值明显高于 OS 长于 14 个月的患者,p=0.002。Cox 回归分析显示,rCBV 和年龄是 OS 的两个最强预测因子(危险比分别为 1.29 和 1.063)。本研究表明,胶质母细胞瘤的血流动力学异常与 mTOR-EGFR 通路的基因组激活状态有关,但增强和增强区的放射基因组学关联不同。rCBV 比单独的基因组生物标志物具有更好的预后价值。

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