Multiplex/combined biomarkers expressed in urine (including PCA3) for early prostate cancer detection; A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer

Laxman B, Morris DS, Yu J, Siddiqui J, Cao J, Mehra R, Lonigro RJ, Tsodikov A, Wei JT, Tomlins SA, Chinnaiyan AM.Cancer Res 2008;68:645-9

• Quantitative PCR analysis of sedimented urine of 234 men presenting for prostate biopsy or radical prostatectomy showed that out of 7 biomarkers and serum prostate specific antigen (PSA), Prostate CAncer gene 3 (PCA3), TMPRSS2:ERG, GOLPH2 and SPINKI could statistically significantly predict the presence of prostate cancer (PCa).
• Of these single biomarkers, only serum PSA and PCA3* are currently clinically available.
• PCA3 outperformed serum prostate specific antigen (PSA) as single biomarker (Table).
• A multiplexed/combined model including these 3 biomarkers plus TMPRSS2:ERG outperformed serum PSA and PCA3 alone.
• The performance of PCA3 was consistent with that in previously published studies.

* Please note that this study did not use the PROGENSA^TM PCA3 Assay which is the only gene-based biomarker currently commercially available in Europe

Table

AUC: area under the receiver operating characteristics curve

Reviewed by

Prof. J. Schalken

Editorial comment

In this manuscript the authors pursue an interesting avenue in biomarker development. Can a panel of markers provide additive values for a given indication? From a bioinformatics analysis these authors identified 4 markers including PCA3. PCA3 was recently introduced as the first prostate cancer specific marker. TMPRSS2erg gene fusions are the most common prostate cancer genetic change. Recently my team1 showed that PCA3 + TMPRSS2erg have the potential to be a very powerful panel. In this study these findings are confirmed, with the addition of two more markers. The four marker panel performs remarkably similar to the two gene panel¹. The further clinical evaluation of PCA3 and TMPRSS-erg based marker panels are very promising.

1). Hessels,D. et al. Detection of TMPRSS2-ERG fusion transcripts and prostate cancer antigen 3 in urinary sediments may improve diagnosis of prostate cancer. Clin Cancer Res 2007;13:5103-5108

More information: http://cancerres.aacrjournals.org/cgi/reprint/68/3/645