High expression of heparanase is significantly associated with dedifferentiation and lymph node metastasis in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA and via HIF1a to HB-EGF and bFGF.
BACKGROUND
Pancreatic cancer still has one of the worst prognoses of all cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. Especially heparanase (HPSE) has recently been discussed as a key factor in pancreatic cancer.


METHODS
Paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma who were scheduled for primary surgical resection. Direct quantitative real-time reverse transcriptase polymerase chain reaction (TaqMan) assays were performed in triplicates to determine HPSE, hypoxia inducible factor-1 alpha (HIF1a), platelet-derived growth factor alpha (PDGFA), heparin-binding EGF-like growth factor (HB-EGF), and basic fibroblast growth factor (bFGF) gene expression levels.


RESULTS
HPSE was significantly correlated to PDGFA (p = 0.04) and HIF1a (p = 0.04). The correlation of HIF1a to bFGF and HB-EGF was significant (p = 0.04, p = 0.02). Stepwise multiple linear regression models showed a significant independent association of HPSE with lymph node metastasis (p = 0.025) and with dedifferentiation (p = 0.042).


CONCLUSIONS
Heparanase seems to be significantly associated with lymph node metastasis (p = 0.025) as well as dedifferentiation (p = 0.042). We assume that HPSE plays a crucial role for the aggressiveness of pancreatic cancer. Larger studies including more patients seem to be warranted.
Hoffmann
Andreas-Claudius
AC
Department of Biochemistry and Molecular Biology and Norris Comprehensive Cancer Center, University of Southern California, 1640 Marengo Street, Suite 600, Los Angeles, CA 90033, USA. ach@o117.com
Mori
Ryutaro
R
Vallbohmer
Daniel
D
Brabender
Jan
J
Drebber
Uta
U
Baldus
Stephan E
SE
Klein
Ellen
E
Azuma
Mizutomo
M
Metzger
Ralf
R
Hoffmann
Christina
C
Hoelscher
Arnulf H
AH
Danenberg
Kathleen D
KD
Prenzel
Klaus L
KL
Danenberg
Peter V
PV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression; D005966:Glucuronidase / Q000235:genetics*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010865:Pilot Projects; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D000099175:Heparanase
D016222:Fibroblast Growth Factor 2; D005966:Glucuronidase; D066257:Heparin-binding EGF-like Growth Factor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D000099175:Heparanase; C587883:HBEGF protein, human; C497442:HIF1A protein, human; C075278:platelet-derived growth factor A