Quantitative multi-gene expression profiling of primary prostate cancer.
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.
Schmidt
Uta
U
Department of Urology, Technical University of Dresden, Germany.
Fuessel
Susanne
S
Koch
Rainer
R
Baretton
Gustavo B
GB
Lohse
Andrea
A
Tomasetti
Silke
S
Unversucht
Susanne
S
Froehner
Michael
M
Wirth
Manfred P
MP
Meye
Axel
A
D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D063151:Polycomb Repressive Complex 2; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050053:TRPM Cation Channels / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D017211:Treatment Failure
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D014157:Transcription Factors; C479341:prostate cancer antigen 3, human; C422655:prostein; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2