Use of multiple biomarkers for a molecular diagnosis of prostate cancer

The identification of biomarkers capable of providing a reliable molecular diagnostic test for prostate cancer (PCa) is highly desirable clinically. We describe here 4 biomarkers, UDP‐N‐Acetyl‐α‐D‐galactosamine transferase (GalNAc‐T3; not previously associated with PCa), PSMA, Hepsin and DD3/PCA3, which, in combination, distinguish prostate cancer from benign prostate hyperplasia (BPH). GalNAc‐T3 was identified as overexpressed in PCa tissues by microarray analysis, confirmed by quantitative real‐time PCR and shown immunohistochemically to be localised to prostate epithelial cells with higher expression in malignant cells. Real‐time quantitative PCR analysis across 21 PCa and 34 BPH tissues showed 4.6‐fold overexpression of GalNAc‐T3 (p = 0.005). The noncoding mRNA (DD3/PCA3) was overexpressed 140‐fold (p = 0.007) in the cancer samples compared to BPH tissues. Hepsin was overexpressed 21‐fold (p = 0.049, whereas the overexpression for PSMA was 66‐fold (p = 0.047). When the gene expression data for these 4 biomarkers was combined in a logistic regression model, a predictive index was obtained that distinguished 100% of the PCa samples from all of the BPH samples. Therefore, combining these genes in a real‐time PCR assay represents a powerful new approach to diagnosing PCa by molecular profiling. (Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html.) © 2004 Wiley‐Liss, Inc.