Christiane  Bruns,A.  Quaas,Christopher Betzler,Dirk  Waldschmidt,Felix  Popp,Florian  Gebauer,Hakan  Alakus,Martin  Maus,Patrick S. Plum,
Differential Gene Expression in Pancreatic Ductal Adenocarcinoma and Stromal Tissue: Prognostic and Therapeutic Implications
Journal of Surgical Oncology
2019
2674-3000
http://dx.doi.org/10.31487/j.JSO.2019.02.11
https://www.sciencerepository.org/differential-gene-expression-in-pancreatic-ductal-adenocarcinoma-and-stromal-tissue-prognostic-and-therapeutic-implications_JSO-2019-2-111 
Abstract: 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.Keywords: Pancreatic ductal adenocarcinoma, stroma, c-MET, resistance, prognosis, gene expression