TY - JOUR
T1 - Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer
AU - Eisenach, P. A.
AU - Soeth, E.
AU - Röder, C.
AU - Klöppel, G.
AU - Tepel, J.
AU - Kalthoff, H.
AU - Sipos, B.
N1 - Funding Information:
This work was partially funded by Merck KGaA (Darmstadt, Germany). We thank Prof. Nigel Hooper (University of Leeds, UK) for donation of the anti-DPEP1 antibody as well as Sonja Vollbehr and Bianca Zinke (Institute for Experimental Cancer Research, UK S-H Campus Kiel, Germany) for technical support. We are furthermore grateful to the late Prof. Siegfried Matzku, who initiated this study with outstanding enthusiasm and expertise. In addition, we thank Prof. Bernd Kremer, former head of the Department of General Surgery, for his clinical and scientific support.
PY - 2013/8/6
Y1 - 2013/8/6
N2 - Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Improvements in the understanding of its molecular mechanism and the characterisation of CRC-specific biomarkers facilitating early detection are considered to increase overall survival. Methods: A meta-analysis of microarray and Serial Analysis of Gene Expression (SAGE) has been performed to identify differentially regulated genes in CRC. Dipeptidase 1 (DPEP1/MDP/RDP) and Syntenin-2 (SDCBP2/SITAC18) were found to be differentially expressed in tumour tissue compared with normal mucosa. Expression of DPEP1 was assessed in a validation set of 87 normal mucosa samples, 20 hyperplastic polyps, 46 CR adenomas with low-and high-grade intraepithelial neoplasia (IEN) and 217 well-documented CRCs by immunohistochemistry and partially by immunoblotting and real-time PCR.Results:Expression of DPEP1 was specifically increased in human CRC tissue samples compared with normal mucosa (P<0.0001, Mann-Whitney U-test), showing a striking upregulation in high-grade compared with low-grade IEN. Furthermore, high DPEP1 expression was found to strongly correlate with histological stage (P<0.0001, chi-square test) as well as localisation (P<0.0001, chi-square test) and has been recognised as an independent adverse prognostic factor, showing significant prognostic values with an ROC (receiver operating characteristic)-AUC of 0.9230. Conclusion: Dipeptidase 1 has been identified as an excellent marker of high-grade IEN and CRC, and may thus be applied for screening of early neoplastic lesions and for prognostic stratification.
AB - Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Improvements in the understanding of its molecular mechanism and the characterisation of CRC-specific biomarkers facilitating early detection are considered to increase overall survival. Methods: A meta-analysis of microarray and Serial Analysis of Gene Expression (SAGE) has been performed to identify differentially regulated genes in CRC. Dipeptidase 1 (DPEP1/MDP/RDP) and Syntenin-2 (SDCBP2/SITAC18) were found to be differentially expressed in tumour tissue compared with normal mucosa. Expression of DPEP1 was assessed in a validation set of 87 normal mucosa samples, 20 hyperplastic polyps, 46 CR adenomas with low-and high-grade intraepithelial neoplasia (IEN) and 217 well-documented CRCs by immunohistochemistry and partially by immunoblotting and real-time PCR.Results:Expression of DPEP1 was specifically increased in human CRC tissue samples compared with normal mucosa (P<0.0001, Mann-Whitney U-test), showing a striking upregulation in high-grade compared with low-grade IEN. Furthermore, high DPEP1 expression was found to strongly correlate with histological stage (P<0.0001, chi-square test) as well as localisation (P<0.0001, chi-square test) and has been recognised as an independent adverse prognostic factor, showing significant prognostic values with an ROC (receiver operating characteristic)-AUC of 0.9230. Conclusion: Dipeptidase 1 has been identified as an excellent marker of high-grade IEN and CRC, and may thus be applied for screening of early neoplastic lesions and for prognostic stratification.
UR - http://www.scopus.com/inward/record.url?scp=84883158184&partnerID=8YFLogxK
U2 - 10.1038/bjc.2013.363
DO - 10.1038/bjc.2013.363
M3 - Article
C2 - 23839495
AN - SCOPUS:84883158184
SN - 0007-0920
VL - 109
SP - 694
EP - 703
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -
