Co-expression of KLK6 and KLK10 as prognostic factors for survival in pancreatic ductal adenocarcinoma.
Kallikreins play an important role in tumour microenvironment and as cancer biomarkers in different cancer entities. Previous studies suggested an upregulation of KLK10 and KLK6 in pancreatic ductal adenocarcinoma (PDAC). Therefore, we evaluated the clinicopathological role of these kallikreins and their value as biomarkers in PDAC.Differential expression was validated by DNA-microarrays and immunohistochemistry in normal and malignant pancreatic tissues. Sera concentrations of both kallikreins were evaluated using ELISA. In silico analysis of possible protein interactions and gene silencing of KLK10 in vitro using siRNAs gave further insights in the pathomechanisms.Gene expression analysis and immunohistochemistry demonstrated a strong expression for KLK10 and KLK6 in PDAC. Statistical analysis showed that co-expression of these kallikreins correlated with an R1-resection status (P=0.017) and worse outcome for overall survival (P=0.031). Multivariate analysis proofed that co-expression is an independent prognostic factor for survival (P=0.043). Importantly, KLK10 knockdown in AsPC-1 cells significantly reduced cell migration, whereas computational analysis suggested interaction of KLK6 with angiogenetic factors as an important mechanism.Co-expression of KLK10 and KLK6 plays an unfavourable role in PDAC. Our results suggest that this effect is likely mediated by an interaction with the factors of the extracellular matrix and enhancement of cancer cell motility.
Rückert
F
F
Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University of Dresden, Fetscherstrasse 74, Dresden 01307, Germany. Felix.Rueckert@uniklinikum-dresden.de
Hennig
M
M
Petraki
C D
CD
Wehrum
D
D
Distler
M
M
Denz
A
A
Schröder
M
M
Dawelbait
G
G
Kalthoff
H
H
Saeger
H-D
HD
Diamandis
E P
EP
Pilarsky
C
C
Grützmann
R
R
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005136:Eye Proteins / Q000502:physiology; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015843:Serpins / Q000502:physiology; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D007610:Kallikreins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C100936:KLK10 protein, human; C103551:KLK6 protein, human