Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 945-953 |
| Number of pages | 9 |
| Journal | Pancreatology |
| Volume | 18 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2018 |
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Gene expression analysis of embryonic pancreas development master regulators and terminal cell fate markers in resected pancreatic cancer: A correlation with clinical outcome. / Dugnani, E; Sordi, V; Pellegrini, S; Chimienti, R; Marzinotto, I; Pasquale, Valentina; Liberati, Daniela; Balzano, G; Doglioni, C; Reni, M; Gandolfi, A; Falconi, M; Lampasona, V; Piemonti, L.
In: Pancreatology, Vol. 18, No. 8, 2018, p. 945-953.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Gene expression analysis of embryonic pancreas development master regulators and terminal cell fate markers in resected pancreatic cancer: A correlation with clinical outcome
AU - Dugnani, E
AU - Sordi, V
AU - Pellegrini, S
AU - Chimienti, R
AU - Marzinotto, I
AU - Pasquale, Valentina
AU - Liberati, Daniela
AU - Balzano, G
AU - Doglioni, C
AU - Reni, M
AU - Gandolfi, A
AU - Falconi, M
AU - Lampasona, V
AU - Piemonti, L
PY - 2018
Y1 - 2018
N2 - 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. © 2018
AB - 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. © 2018
U2 - 10.1016/j.pan.2018.09.006
DO - 10.1016/j.pan.2018.09.006
M3 - Article
VL - 18
SP - 945
EP - 953
JO - Pancreatology
JF - Pancreatology
SN - 1424-3903
IS - 8
ER -