Gene expression analysis of embryonic pancreas development master regulators and terminal cell fate markers in resected pancreatic cancer: A correlation with clinical outcome.

Authors:
Erica Dugnani
Erica Dugnani
San Raffaele Diabetes Research Institute (HSR-DRI)
Italy
Valeria Sordi
Valeria Sordi
San Raffaele Diabetes Research Institute (HSR-DRI)
Silvia Pellegrini
Silvia Pellegrini
University of Pisa
Italy
Raniero Chimienti
Raniero Chimienti
Diabetes Research Institute
Ilaria Marzinotto
Ilaria Marzinotto
Diabetes Research Institute
Valentina Pasquale
Valentina Pasquale
Department of Neuroscience and Brain Technologies
Daniela Liberati
Daniela Liberati
Diabetes Research Institute
Gianpaolo Balzano
Gianpaolo Balzano
University of Verona
Italy

Pancreatology 2018 Dec 25;18(8):945-953. Epub 2018 Sep 25.

Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address:

Background: Despite the recent introduction of new drugs and the development of innovative multi-target treatments, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. Even when PDAC is resectable, the rate of local or widespread disease recurrence remains particularly high. Currently, reliable prognostic biomarkers of recurrence are lacking. We decided to explore the potential usefulness of pancreatic developmental regulators as biomarkers of PDAC relapse.

Methods: We analyzed by quantitative real-time PCR the mRNA of selected factors involved either in pancreatic organogenesis (ISL1, NEUROD1, NGN3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1 and PTF1α) or associated with terminally committed pancreatic cells (CHGA, CHGB, GAD2, GCG, HNF6α, INS, KRT19, SYP) in 17 PDAC cell lines and in frozen tumor samples from 41 PDAC patients.

Results: High baseline levels of the ISL1, KRT19, PAX6 and PDX1 mRNAs in PDAC cell lines, were risk factors for time-dependent xenograft appearance after subcutaneous injection in CD1-Nude mice. Consistently, in human PDAC samples, high levels of KRT19 mRNA were associated with reduced overall survival and earlier recurrence. Higher levels of PDX1 or PAX6 mRNAs were instead associated with a higher frequency of local recurrence.

Conclusions: Our findings suggest that selected factors associated with pancreas development or its terminal differentiation might be implicated in mechanisms of PDAC progression and/or metastatic spread and that the measurement of their mRNA in tumors might be potentially used to improve patient prognostic stratification and prediction of the relapse site.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S14243903183068
Publisher Site
http://dx.doi.org/10.1016/j.pan.2018.09.006DOI Listing
December 2018
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