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-alpha-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.)
Landers
Kelly A
KA
Department of Surgery, Central Clinical Division, School of Medicine, University of Queensland, Herston, Queensland 4072, Australia.
Burger
Michelle J
MJ
Tebay
Michelle A
MA
Purdie
David M
DM
Scells
Betty
B
Samaratunga
Hemamali
H
Lavin
Martin F
MF
Gardiner
Robert A
RA
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D017350:N-Acetylgalactosaminyltransferases / Q000032:analysis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011470:Prostatic Hyperplasia / Q000175:diagnosis* / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D012680:Sensitivity and Specificity; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D014408:Biomarkers, Tumor; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase