Relationship between 18F-FDG uptake on positron emission tomography and molecular biology in malignant pleural mesothelioma
Relationship between 18F-FDG uptake on positron emission tomography and molecular biology in malignant pleural mesothelioma
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DOI：
10.1016/j.ejca.2012.01.016
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发表时间：
2012-05-01
影响因子：
8.4
通讯作者：
Yamamoto, Nobuyuki
中科院分区：
文献类型：
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作者：
Kaira, Kyoichi;Serizawa, Masakuni;Yamamoto, Nobuyuki
背景：2-[F-18]-氟-2-脱氧-d -葡萄糖（F-18- fdg）正电子发射断层扫描（PET）有助于预测恶性胸膜间皮瘤（MPM）的治疗反应和预后。然而，对于这种现象还没有令人满意的生物学解释。本研究的目的是探讨f18 - fdg摄取的潜在生物学机制。方法：21例MPM患者在治疗前接受F-18-FDG PET检查。对肿瘤切片进行葡萄糖转运蛋白1 （Glut1）免疫组化染色；葡萄糖转运蛋白3 (Glut3)；缺氧诱导因子1 α (HIF-1 α)；我己糖激酶;血管内皮生长因子；微血管(CD34);表皮生长因子受体；细胞增殖（Ki-67标记指数）；Akt/ mTOR信号通路（PTEN、p-Akt、p-mTOR和p-S6K）；细胞周期控制（p53和pRb）；凋亡标志物（bcl-2）。我们还进行了间皮瘤细胞系对F-18-FDG摄取的体外研究。结果：F-18-FDG摄取与Glut1 （p < 0.0001）、HIF-1 α (p = 0.006)、己糖激酶I （p = 0.0002）、VEGF （p = 0.0013）、CD34 （p = 0.0001）、Ki-67（p = 0.0047）、mTOR （p = 0.00478）、p53 （p = 0.0004）显著相关。F-18-FDG的高摄取与MPM的不良预后显著相关。我们的体外研究表明，Glut1和HIF-1 α的上调与间皮瘤细胞对F-18-FDG的摄取密切相关，mTOR抑制剂诱导Glut1表达和F-18-FDG摄取的降低。结论：MPM中F-18-FDG的摄取量与糖代谢、葡萄糖磷酸化、缺氧、血管生成、细胞增殖（Ki-67）、细胞周期调节因子和mTOR信号通路的存在有关。(C) 2012 Elsevier Ltd.版权所有。
Background: The usefulness of 2-[F-18]-fluoro-2-deoxy-D-glucose (F-18-FDG) positron emission tomography (PET) can help for predicting the therapeutic response and outcome in malignant pleural mesothelioma (MPM). However, no satisfactory biologic explanation exists for this phenomenon. The aim of this study is to investigate the underlying biologic mechanisms of F-18-FDG uptake.Methods: Twenty-one patients with MPM who underwent F-18-FDG PET before treatment were included in this study. Tumour sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1 alpha); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); cell proliferation (Ki-67 labelling index); Akt/ mTOR signalling pathway (PTEN, p-Akt, p-mTOR and p-S6K); cell cycle control (p53 and pRb); apoptosis marker (bcl-2). We also conducted an in vitro study of F-18-FDG uptake in mesothelioma cell lines.Results: F-18-FDG uptake was significantly correlated with Glut1 (p < 0.0001), HIF-1 alpha (p = 0.006), hexokinase I (p = 0.0002), VEGF (p = 0.0013), CD34 (p = 0.0001), Ki-67(p = 0.0047), mTOR (p = 0.00478) and p53 (p = 0.0004). High uptake of F-18-FDG was significantly associated with poor outcome in MPM. Our in vitro study showed that upregulation of Glut1 and HIF-1 alpha was closely related with F-18-FDG uptake into mesothelioma cell, and mTOR inhibitor induced a decrease in Glut1 expression and F-18-FDG uptake.Conclusion: The amount of F-18-FDG uptake in MPM is determined by the presence of glucose metabolism, phosphorylation of glucose, hypoxia, angiogenesis, cell proliferation (Ki-67), cell cycle regulator, and mTOR signalling pathway. (C) 2012 Elsevier Ltd. All rights reserved.