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动态磁敏感对比增强灌注磁共振成像参数在预测新诊断胶质母细胞瘤患者启动子甲基化及预后价值中的应用

Dynamic susceptibility contrast‑enhanced perfusion magnetic resonance imaging parameters for predicting promoter methylation and prognostic value in newly diagnosed patients with glioblastoma.

作者信息

Chida Daiki, Okita Yoshiko, Utsugi Reina, Kuroda Hideki, Hirayama Ryuichi, Kijima Noriyuki, Arisawa Atsuko, Kagawa Naoki, Kanemura Yonehiro, Yoshimura Shinichi, Tomiyama Noriyuki, Kishima Haruhiko

机构信息

Department of Neurosurgery, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan.

Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.

出版信息

Oncol Lett. 2024 Oct 14;28(6):610. doi: 10.3892/ol.2024.14741. eCollection 2024 Dec.

Abstract

O6-methylguanine DNA methyltransferase promoter methylation is an important clinical biomarker of newly diagnosed glioblastoma. Previous radiological studies using dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion have aimed to predict methylation status non-invasively in gliomas with radiological characteristics. The possibility of predicting methylation status using DSC-MRI perfusion with a radiological approach remains controversial. The present study aimed to evaluate the usefulness of MRI perfusion parameters as non-invasive markers to predict methylation status and prognosis in newly diagnosed glioblastoma patients. Thus, 50 patients with histologically confirmed primary glioblastoma, -wildtype who underwent tumor resection at Osaka University Hospital (Suita, Japan) between January 2017 and January 2023 were included in this study. The mean cerebral blood volume (CBV) ratio (rCBV) and cerebral blood flow (CBF) ratio (rCBF) for tumors with methylation (mean rCBV:2.09 and mean rCBF:3.08) were significantly higher compared with those for tumors without methylation (mean rCBV:1.33 and mean rCBF:1.85; P<0.05). While patients with methylation had longer progression-free survival (PFS) compared with those without methylation (P<0.05), there was no significant difference in OS with or without methylation (P=0.06). By contrast, there was no association between MRI perfusion parameters and OS or PFS in patients with glioblastoma. Furthermore, the association between CBV, CBF, promotor methylation status, OS, and PFS were explored. There was no significant prognostic difference between low vascularity tumors (rCBV <1.3 or rCBF <1.8) with or without methylation. On the other hand, high vascularity tumors (rCBF ≥1.8) with promotor methylation were associated to longer OS and PFS compared with those without. However, there was no association between methylation status and OS or PFS in patients with high rCBV (rCBV ≥1.3). The present study indicated that CBV and CBF could be used to predict the methylation status in glioblastomas. However, the prognostic value of tumor vascularity and methylation status may be limited.

摘要

O6-甲基鸟嘌呤DNA甲基转移酶启动子甲基化是新诊断胶质母细胞瘤的一项重要临床生物标志物。以往使用动态磁敏感对比增强(DSC)磁共振成像(MRI)灌注的影像学研究旨在通过肿瘤的影像学特征对胶质瘤的甲基化状态进行无创预测。采用DSC-MRI灌注结合影像学方法预测甲基化状态的可能性仍存在争议。本研究旨在评估MRI灌注参数作为无创标志物在预测新诊断胶质母细胞瘤患者甲基化状态及预后方面的作用。因此,本研究纳入了2017年1月至2023年1月期间在日本大阪大学医院(吹田市)接受肿瘤切除的50例组织学确诊为原发性胶质母细胞瘤-wildtype患者。甲基化肿瘤的平均脑血容量(CBV)比值(rCBV)和脑血流量(CBF)比值(rCBF)(平均rCBV:2.09,平均rCBF:3.08)显著高于未甲基化肿瘤(平均rCBV:1.33,平均rCBF:1.85;P<0.05)。甲基化患者的无进展生存期(PFS)长于未甲基化患者(P<0.05),但甲基化与否的总生存期(OS)无显著差异(P=0.06)。相比之下,胶质母细胞瘤患者的MRI灌注参数与OS或PFS之间无关联。此外,还探讨了CBV、CBF、启动子甲基化状态、OS和PFS之间的关联。低血管性肿瘤(rCBV<1.3或rCBF<1.8)无论有无甲基化,预后均无显著差异。另一方面,启动子甲基化的高血管性肿瘤(rCBF≥1.8)与未甲基化的高血管性肿瘤相比,OS和PFS更长。然而,高rCBV(rCBV≥1.3)患者的甲基化状态与OS或PFS之间无关联。本研究表明,CBV和CBF可用于预测胶质母细胞瘤的甲基化状态。然而,肿瘤血管性和甲基化状态的预后价值可能有限。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72e5/11528182/1f981c5a5e41/ol-28-06-14741-g00.jpg

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