Differential Gene Expression in Pancreatic Ductal Adenocarcinoma and Stromal Tissue: Prognostic and Therapeutic Implications

Author Info

Christiane Bruns A. Quaas Christopher Betzler Dirk Waldschmidt Felix Popp Florian Gebauer Hakan Alakus Martin Maus Patrick S. Plum

Corresponding Author

Christopher Betzler
Department of General, Visceral, and Tumor Surgery, University of Cologne, 50937 Cologne, Germany

A B S T R A C T

Background: Pancreatic ductal adenocarcinoma is one of the most aggressive solid malignancies. The cMET oncogene plays a crucial role in mediating local invasion, systemic dissemination and resistance in this cancer. The genetic makeup of surrounding stromal tissue has shown to be relevant for drug delivery in pancreatic cancer as exemplified by nab-paclitaxel binding to the stromal protein SPARK. In this study we investigated c-MET, ENT1, EREG, GLUT1 and RRM1 mRNA expression patterns in pancreatic ductal adenocarcinoma and stromal tissue in patients with clinical outcome. Methods: FFPE tumor specimens from patients with resectable pancreatic cancer that underwent surgery and adjuvant chemotherapy with gemcitabine were evaluated. C-MET, ENT1, EREG, GLUT1 and RRM1 mRNA expression results could be obtained for 25, 25, 20, 25, 21 cases in tumor and 19, 21, 14, 20, 14 cases in stromal tissue as not all samples were sufficient in quality and quantity for microdissection and mRNA analysis. Specifically, designed primers and probes were used to detect mRNA c-MET, ENT1, EREG, GLUT1 and RRM1 expression levels by quantitative RT-PCR in reference to beta-actin. Results: C-MET, ENT1, EREG, GLUT1 and RRM1 mRNA expression was significantly divergent between pancreatic stromal and tumor tissue (p<0.0001, p<0.001, p<0.004, p<0.0001, p=0.48). When statistically evaluated for the best cut-off, patients with high (>5.00) c-MET expression in the tumor tissue had a worse overall survival (p<0.003). ENT1, EREG, GLUT1 and RRM1 expression in the tumor tissue also influenced the overall survival (p=0.398, p=0.106, p=0.050, p=0.199). C-MET mRNA expression in stromal tissue did not correlate with outcome. Conclusions: According to our data high c-MET expression is a negative prognostic indicator for pancreatic cancer. Further studies have to evaluate if c-MET expression may predict response to new c-MET inhibitors like cabozantinib. The role of c-MET expression in pancreatic stromal tissue needs further investigation.

Article Info

Article Type

Research Article

Publication history

Received: Fri 07, Jun 2019
Accepted: Wed 19, Jun 2019
Published: Fri 28, Jun 2019

Copyright

© 2023 Christopher Betzler. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.JSO.2019.02.11