Hepsin is highly over expressed in and a new candidate for a prognostic indicator in prostate cancer.

PURPOSE Other cDNA microarray studies have shown that hepsin is one of the highly over expressed genes in prostate cancer tissue compared with nonmalignant and benign prostatic hyperplasia tissue. We quantitatively analyzed hepsin gene expression with real-time polymerase chain reaction and calculated its relationships with clinicopathological parameters in a large cohort of samples. MATERIALS AND METHODS Matched prostate tissue samples from the cancerous and noncancerous parts of the same prostates were obtained from 90 patients with prostate cancer who underwent radical prostatectomy. Quantitative reverse transcriptase-polymerase chain reaction was performed using LightCycler Fast Start DNA Master SYBR Green I on a LightCycler (Roche Diagnostics GmbH, Mannheim, Germany) system. The ratio of hepsin-to-beta-actin (a housekeeping gene) was used to normalize data. RESULTS Hepsin over expression in cancerous compared with noncancerous tissue was found in 81 of the 90 patient samples (90%, p <0.001). In 48 patients (53%) hepsin over expression was more than 10-fold in cancerous tissue. The ratio of cancerous-to-noncancerous hepsin expression was significantly higher in the 39 patients with grade 3 tumors compared with the 51 with grade 2 tumors (median 15.5 vs 9.6, p = 0.031). For the prognosis a cutoff at the 75th percentile provided a significant difference between patients at lower risk (pT2, G2 and Gleason score less than 7) and higher risk (pT3/4, G3 and Gleason score 7 or greater) for relapse. CONCLUSIONS This report of the quantitative analysis of hepsin expression, which is the first to our knowledge, shows strong and significant over expression in prostate cancer tissue. Hepsin expression may be a new prognostic marker that could be used for assessing prostate cancer aggressiveness.

[1]  K. Kurachi,et al.  A novel trypsin-like serine protease (hepsin) with a putative transmembrane domain expressed by human liver and hepatoma cells. , 1988, Biochemistry.

[2]  O. Nilsson,et al.  Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. , 1991, Clinical chemistry.

[3]  K. Kurachi,et al.  Hepsin, a cell membrane-associated protease. Characterization, tissue distribution, and gene localization. , 1991, The Journal of biological chemistry.

[4]  Characterization of hepsin, a membrane bound protease. , 1991, Biomedica biochimica acta.

[5]  U. Stenman,et al.  A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. , 1991, Cancer research.

[6]  K. Kurachi,et al.  Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[7]  W. Kisiel,et al.  Hepsin, a Putative Membrane-associated Serine Protease, Activates Human Factor VII and Initiates a Pathway of Blood Coagulation on the Cell Surface Leading to Thrombin Formation (*) , 1995, The Journal of Biological Chemistry.

[8]  K. Jung,et al.  Factors influencing the ratio of free to total prostate‐specific antigen in serum , 1997, International journal of cancer.

[9]  U J Balis,et al.  The LightCycler: a microvolume multisample fluorimeter with rapid temperature control. , 1997, BioTechniques.

[10]  T. Vu,et al.  Identification and Cloning of the Membrane-associated Serine Protease, Hepsin, from Mouse Preimplantation Embryos* , 1997, The Journal of Biological Chemistry.

[11]  K. Shigemasa,et al.  Hepsin, a cell surface serine protease identified in hepatoma cells, is overexpressed in ovarian cancer. , 1997, Cancer research.

[12]  W. Kisiel,et al.  Expression of the Factor VII Activating Protease, Hepsin, in situ in Renal Cell Carcinoma , 1998, Thrombosis and Haemostasis.

[13]  J. Oesterling,et al.  Prostate specific antigen: a decade of discovery--what we have learned and where we are going. , 1999, The Journal of urology.

[14]  J. Trachtenberg,et al.  Serum human glandular kallikrein-2 protease levels predict the presence of prostate cancer among men with elevated prostate-specific antigen. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  Jeffrey A. Magee,et al.  Expression profiling reveals hepsin overexpression in prostate cancer. , 2001, Cancer research.

[16]  T. Stamey.  Preoperative serum prostate-specific antigen (PSA) below 10 microg/l predicts neither the presence of prostate cancer nor the rate of postoperative PSA failure. , 2001, Clinical chemistry.

[17]  J. Welsh,et al.  Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. , 2001, Cancer research.

[18]  S. Dhanasekaran,et al.  Delineation of prognostic biomarkers in prostate cancer , 2001, Nature.

[19]  T. Stamey,et al.  Molecular genetic profiling of Gleason grade 4/5 prostate cancers compared to benign prostatic hyperplasia. , 2001, The Journal of urology.

[20]  D. Katsaros,et al.  Quantitative expression of the human kallikrein gene 9 (KLK9) in ovarian cancer: a new independent and favorable prognostic marker. , 2001, Cancer research.

[21]  Caroline Joyce,et al.  Quantitative RT-PCR. A review of current methodologies. , 2002, Methods in molecular biology.

[22]  Ian M Thompson,et al.  Prostate‐specific antigen: A review of the validation of the most commonly used cancer biomarker , 2004, Cancer.