Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, China.
Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu, China.
Nucl Med Biol. 2021 May-Jun;96-97:27-34. doi: 10.1016/j.nucmedbio.2021.02.006. Epub 2021 Mar 11.
Due to individual deviations in tumor tissue uptake, the role of [F]fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) in hepatocellular carcinoma (HCC) diagnosis is limited. β-Hydroxy β-methylglutaryl-CoA reductase degradation 1 (HRD1) plays a key role in clearing misfolded proteins. This study is aimed to investigate the role and mechanism of HRD1 in [F]FDG uptake for the diagnosis of HCC.
HRD1 expression level was detected using immunohistochemical (IHC) staining in 9 HCC patients. [F]FDG PET/CT scans were conducted before treatment. [F]FDG uptakes in HRD1 overexpressed and knockdown transgenic models were measured by γ-counter and microPET imaging. The GLUT1-HRD1 complex was examined by co-immunoprecipitation and IHC assays. GLUT1 expression in different cell lines, xenograft models and HCC patients was evaluated by Western blot and IHC assays.
HRD1 was highly expressed in the HCC tumors of patients with low [F]FDG uptake, while the HRD1 expression was obviously low in the higher [F]FDG uptake group. Both in vitro and in vivo studies found that HRD1 significantly inhibited [F]FDG uptake in HCC Huh7 cell lines and animal models. Furthermore, the co-location and interaction of HRD1 with GLUT1 were detected, and the results also indicate that HRD1 could induce the degradation of GLUT1 in vitro and in vivo.
HRD1 inhibits the high uptake of [F]FDG in HCC tumor cells by inducing degradation of GLUT1, which leads to decreased diagnostic efficiency of [F]FDG PET imaging for HCC.
This study suggests that HRD1 inhibits the high uptake of [F]FDG in HCC tumor by inducing degradation of GLUT1.
HCC diagnosis with [F]FDG PET should be accompanied by determination of HRD1 expression, and patients with high tumor HRD1 expression might be unsuitable for [F]FDG PET.
由于肿瘤组织摄取存在个体差异，[F]氟脱氧葡萄糖([F]FDG)正电子发射断层扫描(PET)在肝细胞癌(HCC)诊断中的作用有限。β-羟-β-甲基戊二酰基辅酶 A 还原酶降解 1(HRD1)在清除错误折叠的蛋白质中发挥关键作用。本研究旨在探讨 HRD1 在[F]FDG摄取中的作用和机制，以用于 HCC 的诊断。
采用免疫组织化学(IHC)染色法检测 9 例 HCC 患者肿瘤组织中 HRD1 的表达水平。治疗前进行[F]FDG PET/CT 扫描。通过γ计数器和 microPET 成像测量 HRD1 过表达和敲低转基因模型中的[F]FDG 摄取。通过免疫共沉淀和 IHC 检测 GLUT1-HRD1 复合物。通过 Western blot 和 IHC 检测不同细胞系、异种移植模型和 HCC 患者中 GLUT1 的表达。
低[F]FDG 摄取 HCC 肿瘤患者的 HRD1 表达较高，而高[F]FDG 摄取组 HRD1 表达明显较低。体外和体内研究均发现 HRD1 可显著抑制 HCC Huh7 细胞系和动物模型中的[F]FDG 摄取。此外，还检测到 HRD1 与 GLUT1 的共定位和相互作用，结果还表明 HRD1 可在体外和体内诱导 GLUT1 的降解。
HRD1 通过诱导 GLUT1 降解抑制 HCC 肿瘤细胞对[F]FDG 的高摄取，从而降低[F]FDG PET 成像对 HCC 的诊断效率。
本研究表明 HRD1 通过诱导 GLUT1 降解抑制 HCC 肿瘤对[F]FDG 的高摄取。
[F]FDG PET 用于 HCC 诊断时应同时测定 HRD1 的表达，肿瘤 HRD1 高表达的患者可能不适合[F]FDG PET。
