Quantitative multi-gene expression profiling of primary prostate cancer.

Abstract

BACKGROUND:

This study describes the evaluation of the expression patterns of prostate-related transcripts in 106 matched prostate tissues from prostatectomies as predictors for prostate cancer (PCa).

METHODS:

Quantitative PCR (QPCR) assays with site-specific hybridization probes were established for four housekeeping genes (GAPDH, HPRT, PBGD, TBP) and nine prostate-related genes (AibZIP, D-GPCR, EZH2, PCA3, PDEF, prostein, PSA, PSCA, TRPM8).

RESULTS:

The relative mRNA expression levels of AibZIP, D-GPCR, EZH2, PCA3, PDEF, PSA, TRPM8 (all P < 0.001) and prostein (P = 0.019) normalized to the TBP reference gene were significantly higher in malignant compared to non-malignant prostate tissues. Employing receiver-operating characteristic (ROC) analyses, PCA3 was the best single tumor marker with the highest area-under-the-curve (AUC = 0.85). A multivariate logit model for the predictability of the tumor was developed, which employed the relative expression levels of EZH2, PCA3, prostein, and TRPM8 and yielded an AUC of 0.90.

CONCLUSIONS:

The transcript marker PCA3 is a powerful predictor of primary PCa but the inclusion of EZH2, prostein, and TRPM8 adds even more to the diagnostic power. The finding of a significantly higher mRNA expression of three different genes (prostein, PSA, TRPM8) in organ-confined tumors compared to non-organ-confined tumors as well as the multi-marker PCa prediction model developed in the retrospective model system on prostatectomies could be of clinical importance for diagnostic purposes, and should be verified in diagnostic biopsies.

• Authors: Uta Schmidt, Susanne Fuessel, Rainer Koch, Gustavo B Baretton, Andrea Lohse, Silke Tomasetti, Susanne Unversucht, Michael Froehner, Manfred P Wirth, Axel Meye
• Journal: The Prostate (Prostate) Vol. 66 Issue 14 Pg. 1521-34 (Oct 01 2006) ISSN: 0270-4137 [Print] United States
• PMID: 16921506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2006 Wiley-Liss, Inc.

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• DNA-Binding Proteins
• Membrane Proteins
• RNA, Messenger
• TRPM Cation Channels
• TRPM8 protein, human
• Transcription Factors
• prostate cancer antigen 3, human
• prostein
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein
• Polycomb Repressive Complex 2

Topics

• Aged
• Antigens, Neoplasm (genetics)
• Biomarkers, Tumor (genetics)
• Biopsy
• Cell Line, Tumor
• DNA-Binding Proteins (genetics)
• Enhancer of Zeste Homolog 2 Protein
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genetic Testing (methods)
• Humans
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Multivariate Analysis
• Polycomb Repressive Complex 2
• Predictive Value of Tests
• Prostatic Neoplasms (genetics, pathology, therapy)
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• TRPM Cation Channels (genetics)
• Transcription Factors (genetics)
• Treatment Failure