交界性上皮性卵巢肿瘤通过谷氨酰胺途径致1H-MRS NAA峰增高的代谢机制研究
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中文摘要
常规MR和术中冰冻切片无法准确鉴别交界性(BEOT)和恶性上皮卵巢肿瘤(MEOT),致年轻BEOT患者接受激进手术失去生育能力。前期MRS研究发现BEOT的NAA峰显著增高,MEOT的Cho峰显著增高,NAA/Cho鉴别准确性达100%。NAA量与其碳源谷氨酰胺(Gln)代谢密切相关,推测BEOT NAA峰显著增高原因是肿瘤高度依赖Gln代谢,而MEOT依赖糖酵解。我们拟在已建立的两类肿瘤大鼠模型上,行18F-FDG/FGln PET/CT和MRS扫描,比较两类肿瘤代谢影像表现差异及其相关性;离体瘤组织行色谱质谱、高分辨率核磁共振氢谱代谢组学和生物信息学分析,肿瘤细胞行同位素标记示踪,多层次和角度验证两类肿瘤的代谢通路差异、BEOT的Gln依赖性和MEOT的糖酵解依赖性,阐明两类肿瘤MRS上不同表现的机制,探讨NAA作为BEOT特异性影像标志物的可行性,并为监测靶向药物疗效提供代谢学基础。
英文摘要
Borderline epithelial ovarian tumor (BEOT) is low-grade malignant and its treatment is different from malignant epithelial ovarian tumor (MEOT). Conventional MRI and intraoperative frozen sections are not able to accurately distinguish them, which lead to radical surgeries and fertility loss in young patients with BEOT. Our previous clinical studies of proton magnetic resonance spectroscopy (1H-MRS) showed that N-acetylaspartate (NAA) and choline (Cho) significantly increased in BEOT and MEOT, respectively. The diagnostic accuracy of NAA/Cho in differentiating them was 100%. The content of NAA is closely related to the metabolism of its carbon source-glutamine (Gln). We suppose that the significantly increaseed NAA peak of BEOT is highly dependent on Gln metabolism, while the significantly increaseed Cho peak of MEOT is dependent on glycolysis metabolism. Basing on our established BEOT and MEOT rat models, we intend to perform 18F-FDG and 18F-FGln PET/CT and 1H-MRS scannings to compare the differences in uptake rate and metabolites between the two types of tumors and to investigate their correlation. Also we plan to investigate the difference of metabolic pathways between the two types of tumor tissues by using gas chromatography-mass spectroscopy, high resolution proton nuclear MRS metabolomics and bioinformatics; between the two types of tumor cells by using isotopic tracer method. In multi-level and multi-angle perspective, we will verify the Gln metabolic dependence of BEOT and the glycolysis metabolic dependence of MEOT and elucidate the formation mechanism of different metabolites on 1H-MRS. We intend to explore the feasibility of NAA as a specific imaging marker for BEOT and to provide metabolic basis for monitoring the efficacy of targeted drugs.
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DOI:10.1007/s00330-023-09552-w
发表时间:2023-03
期刊:European Radiology
影响因子:5.9
作者:Haiming Li;S. Cai;Lin Deng;Zebin Xiao;Q. Guo;J. Qiang;J. Gong;Yajia Gu;Zaiyi Liu
通讯作者:Haiming Li;S. Cai;Lin Deng;Zebin Xiao;Q. Guo;J. Qiang;J. Gong;Yajia Gu;Zaiyi Liu
DOI:10.1007/s00330-023-09685-y
发表时间:2023-05-12
期刊:EUROPEAN RADIOLOGY
影响因子:5.9
作者:Lin,Zijing;Wang,Ting;Li,Haiming
通讯作者:Li,Haiming
DOI:10.1002/jmri.27037
发表时间:2020-01-10
期刊:JOURNAL OF MAGNETIC RESONANCE IMAGING
影响因子:4.4
作者:He, Mengge;Song, Yang;Qiang, Jinwei
通讯作者:Qiang, Jinwei
DOI:10.1007/s00330-020-07099-8
发表时间:2020-08-04
期刊:EUROPEAN RADIOLOGY
影响因子:5.9
作者:Yan, Bi Cong;Li, Ying;Qiang, Jin Wei
通讯作者:Qiang, Jin Wei
DOI:10.3389/fonc.2022.894918
发表时间:2022
期刊:FRONTIERS IN ONCOLOGY
影响因子:4.7
作者:Liu, Xue-Fei;Yan, Bi-Cong;Li, Ying;Ma, Feng-Hua;Qiang, Jin-Wei
通讯作者:Qiang, Jin-Wei
基于磁共振功能影像的定量生物标志物研究交界性上皮性卵巢肿瘤的生物学特性
- 批准号:81471628
- 项目类别:面上项目
- 资助金额:72.0万元
- 批准年份:2014
- 负责人:强金伟
- 依托单位:
微小肺癌致支气管、血管形态改变的微型CT和病理机制研究
- 批准号:81171340
- 项目类别:面上项目
- 资助金额:58.0万元
- 批准年份:2011
- 负责人:强金伟
- 依托单位:
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