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F-氟脱氧葡萄糖摄取可预测肺腺癌中的MET表达。

F-fluorodeoxyglucose uptake predicts MET expression in lung adenocarcinoma.

作者信息

An Shuxian, Zhou Xiang, Liu Jianjun, Huang Gang

机构信息

Department of Nuclear Medicine.

Institute of Clinical Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University.

出版信息

Onco Targets Ther. 2017 Nov 27;10:5643-5651. doi: 10.2147/OTT.S150334. eCollection 2017.

Abstract

OBJECTIVE

MET is a member of the receptor tyrosine kinases. Several MET-targeting inhibitors and antagonistic antibodies have shown promising data in clinical trials of lung adenocarcinoma. Finding noninvasive diagnostic tools to estimate the status of MET is helpful in clinical practice. F-fluorodeoxyglucose positron emission tomography/computerized tomography (F-FDG PET/CT) has been used routinely for the diagnosis and staging of tumors. However, the relationship between MET expression and F-FDG uptake has not been investigated yet. This study aimed to determine the correlation of MET expression with F-FDG uptake on PET-CT scan and whether or not F-FDG PET/CT can be used to predict the MET status of lung adenocarcinoma patients.

PATIENTS AND METHODS

Fifty-seven lung adenocarcinoma patients were analyzed in our study. Maximum standardized uptake value (SUV) was calculated in all PET/CT images. The expression levels of MET and two important glycolysis-related markers, glucose transporter 1 (GLUT1) and pyruvate kinase M2, were analyzed by immunohistochemistry of tissues. Spearman rank correlation was used to analyze the association between MET expression and SUV. In vitro MET knockdown in lung adenocarcinoma cells was used to examine the role of MET in tumor metabolism. The effect of MET on GLUT1 expression was investigated using Western blot assay and quantitative polymerase chain reaction.

RESULTS

SUV was positively correlated with the expression levels of MET (=0.458; <0.001) and GLUT1 (=0.551; <0.001). SUV was significantly higher in patients with positive MET expression than in those with negative MET expression (9.92±6.62 vs 4.60±3.00; =0.002). MET knockdown in lung adenocarcinoma cells led to a significant decrease in GLUT1 expression and F-FDG uptake.

CONCLUSION

MET could increase F-FDG uptake by upregulating GLUT1 expression. F-FDG PET/CT could be used to predict the MET status of lung adenocarcinoma patients and to supply valuable information to guide targeted therapy.

摘要

目的

MET是受体酪氨酸激酶家族成员之一。几种靶向MET的抑制剂和拮抗抗体在肺腺癌临床试验中已显示出有前景的数据。寻找非侵入性诊断工具来评估MET状态对临床实践有帮助。F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(F-FDG PET/CT)已常规用于肿瘤的诊断和分期。然而,MET表达与F-FDG摄取之间的关系尚未得到研究。本研究旨在确定PET-CT扫描上MET表达与F-FDG摄取的相关性,以及F-FDG PET/CT是否可用于预测肺腺癌患者的MET状态。

患者与方法

本研究分析了57例肺腺癌患者。在所有PET/CT图像上计算最大标准化摄取值(SUV)。通过组织免疫组化分析MET以及两个重要的糖酵解相关标志物葡萄糖转运蛋白1(GLUT1)和丙酮酸激酶M2的表达水平。采用Spearman等级相关性分析MET表达与SUV之间的关联。在肺腺癌细胞中进行体外MET敲低以研究MET在肿瘤代谢中的作用。使用蛋白质免疫印迹法和定量聚合酶链反应研究MET对GLUT1表达的影响。

结果

SUV与MET(=0.458;<0.001)和GLUT1(=0.551;<0.001)的表达水平呈正相关。MET表达阳性患者的SUV显著高于MET表达阴性患者(9.92±6.62 vs 4.60±3.00;=0.002)。肺腺癌细胞中的MET敲低导致GLUT1表达和F-FDG摄取显著降低。

结论

MET可通过上调GLUT1表达增加F-FDG摄取。F-FDG PET/CT可用于预测肺腺癌患者的MET状态,并为指导靶向治疗提供有价值的信息。

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