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

Purpose: 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). Methods: 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. Results: We observed a significant positive rank correlation between the ADC and the E-cadherin Allred score (rho = 0.553, p < 0.001) and significant negative rank correlations between the ADC and the Runx2 Allred score (rho = -0.526, p < 0.001) as well as the Zeb1 Allred score (rho = -0.710, p < 0.001). Compared to tumors with low ADC values < 1.3 mu m(2)/s, tumors with ADC values >= 1.3 mu m(2)/s had significantly higher Allred scores for E-cadherin (median, 4 versus 5; p < 0.001) and significantly lower Allred scores for Runx2 (median, 3 versus 2; p = 0.003) as well as Zeb1 (median, 4 versus 0; p < 0.001). Conclusion: 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.

Automated summary

This study evaluated the potential of DW-MRI as an imaging biomarker for EMT in PDAC, finding significant correlations between ADC values and expression profiles of E-cadherin, Runx2, and Zeb1. Tumors with higher ADC values showed higher E-cadherin expression and lower Runx2 and Zeb1 expression, indicating a potential role for personalized EMT-targeted therapies based on DW-MRI findings in PDAC patients.