Hepsin is Highly Over Expressed in and a New Candidate for a Prognostic Indicator in Prostate Cancer

Abstract

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. 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. 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. 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.