Lin Wei, Dai Shu-hui, Chen Tao, Kawai Nobuyuki, Miyake Keisuke, Okada Masaki, Haba Reiji, Yamamoto Yuka, Tamiya Takashi, Fei Zhou
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Cell Physiol Biochem. 2016;38(2):635-45. doi: 10.1159/000438656. Epub 2016 Feb 8.
BACKGROUND/AIMS: The nucleolar 58-kDa microspherule protein (MSP58) has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT) has emerged as a promising positron emission tomography (PET) tracer for evaluating tumor malignancy and cell proliferation.
In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas.
The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P < 0.001). The IRS of MSP58 in the tumor showed a highly significant positive correlation with corresponding FLT uptake value (r = 0.61, P < 0.001). The correlation between MSP58 expression and glioma malignancy was also confirmed by immunofluorescence, RT-PCR and western blot analysis. FLT uptake value also exhibited a highly significant positive correlation with the Ki-67 index (r = 0.59, P < 0.001). Kaplan-Meier analysis revealed that MSP58 expression has a significant prognostic ability for the overall survival time similar to that found in the uptake value of FLT-PET.
These results indicate that MSP58 plays an important role in cell proliferation and will be one of the potential candidates of molecular therapy targeting proliferation. FLT-PET might be used as an early measure of treatment response in the proliferation-targeted therapy.
背景/目的:核仁58 kDa微球蛋白(MSP58)具有重要的转录调控功能,在癌症的发生和发展中起关键作用。3'-脱氧-3'-[18F]氟胸苷(FLT)已成为一种有前景的正电子发射断层扫描(PET)示踪剂,用于评估肿瘤恶性程度和细胞增殖。
在本研究中,采用免疫组织化学法评估55例不同分级胶质瘤患者的MSP58表达,并使用FLT-PET检查相应的PET图像。
MSP58的免疫反应性评分(IRS)随肿瘤分级增加而升高,IV级胶质瘤表达最高,且与Ki-67指数呈高度显著正相关(r = 0.65,P < 0.001)。肿瘤中MSP58的IRS与相应的FLT摄取值呈高度显著正相关(r = 0.61,P < 0.001)。免疫荧光、RT-PCR和蛋白质印迹分析也证实了MSP58表达与胶质瘤恶性程度之间的相关性。FLT摄取值与Ki-67指数也呈高度显著正相关(r = 0.59,P < 0.001)。Kaplan-Meier分析显示,MSP58表达对总生存时间具有显著的预后能力,类似于FLT-PET摄取值。
这些结果表明,MSP58在细胞增殖中起重要作用,将成为增殖靶向分子治疗的潜在候选物之一。FLT-PET可能用作增殖靶向治疗中治疗反应的早期指标。