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胰腺癌中的上皮-间质转化与扩散加权磁共振成像中受限的水扩散相关。

Epithelial-to-Mesenchymal Transition in Pancreatic Cancer is associated with Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging.

作者信息

Mayer Philipp, Kraft Anne, Roth Wilfried, Hackert Thilo, Bergmann Frank, Kauczor Hans-Ulrich, Steinle Verena, Khristenko Ekaterina, Klauss Miriam, Gaida Matthias M

机构信息

Clinic for Diagnostic and Interventional Radiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.

Institute of Pathology, University Medical Center Mainz, JGU-Mainz, 55131 Mainz, Germany.

出版信息

J Cancer. 2021 Nov 4;12(24):7488-7497. doi: 10.7150/jca.63633. eCollection 2021.

Abstract

This study aimed to evaluate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) as imaging biomarker for epithelial-to-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC). In forty-two patients, preoperative apparent diffusion coefficient (ADC) values of therapy-naive PDAC were compared with immunohistochemical expression profiles of the epithelial marker E-cadherin as well as mesenchymal transcription factors Runt-related transcription factor 2 (Runx2) and Zinc finger E-box-binding homeobox 1 (Zeb1), as determined by Allred immunoreactivity score. We observed a significant positive rank correlation between the ADC and the E-cadherin Allred score (ρ = 0.553, p < 0.001) and significant negative rank correlations between the ADC and the Runx2 Allred score (ρ = -0.526, p < 0.001) as well as the Zeb1 Allred score (ρ = -0.710, p < 0.001). Compared to tumors with low ADC values < 1.3 µm/s, tumors with ADC values ≥ 1.3 µm/s had significantly higher Allred scores for E-cadherin (median, 4 5; p < 0.001) and significantly lower Allred scores for Runx2 (median, 3 2; p = 0.003) as well as Zeb1 (median, 4 0; p < 0.001). In PDAC, tumor plasticity in terms of EMT is well reflected by ADC values from DW-MRI. In the near future, DW-MRI could be beneficial for identification of PDAC patients that might profit from personalized EMT-targeted therapies.

摘要

本研究旨在评估扩散加权磁共振成像(DW-MRI)作为胰腺导管腺癌(PDAC)上皮-间质转化(EMT)成像生物标志物的潜力。在42例患者中,将未经治疗的PDAC的术前表观扩散系数(ADC)值与上皮标志物E-钙黏蛋白以及间充质转录因子Runx相关转录因子2(Runx2)和锌指E盒结合同源框1(Zeb1)的免疫组化表达谱进行比较,后者通过Allred免疫反应性评分来确定。我们观察到ADC与E-钙黏蛋白Allred评分之间存在显著的正等级相关性(ρ = 0.553,p < 0.001),ADC与Runx2 Allred评分(ρ = -0.526,p < 0.001)以及Zeb1 Allred评分(ρ = -0.710,p < 0.001)之间存在显著的负等级相关性。与ADC值<1.3 µm/s的低ADC值肿瘤相比,ADC值≥1.3 µm/s的肿瘤E-钙黏蛋白的Allred评分显著更高(中位数,4对5;p < 0.001),Runx2(中位数,3对2;p = 0.003)和Zeb1(中位数,4对0;p < 0.001)的Allred评分显著更低。在PDAC中,DW-MRI的ADC值很好地反映了EMT方面的肿瘤可塑性。在不久的将来,DW-MRI可能有助于识别可能从个性化EMT靶向治疗中获益的PDAC患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aee7/8734418/573145e49aad/jcav12p7488g001.jpg

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