Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers

Matthew J Roberts; Renee S Richards; Clement W K Chow; Suhail A R Doi; Horst Joachim Schirra; Marion Buck; Hemamali Samaratunga; Joanna Perry-Keene; Diane Payton; John Yaxley; Martin F Lavin; Robert A Gardiner

doi:10.1016/j.prnil.2016.04.002

Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers

Prostate Int. 2016 Sep;4(3):97-102. doi: 10.1016/j.prnil.2016.04.002. Epub 2016 May 5.

Authors

Affiliations

¹ The University of Queensland, Division of Surgery, School of Medicine, Brisbane, QLD, Australia; The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia; The University of Queensland, Centre for Advanced Imaging, Brisbane, QLD, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
² The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia.
³ Research School of Population Health, The Australian National University, Canberra, Australia; School of Agricultural, Computational and Environmental Sciences, University of Southern Queensland, Toowoomba, Australia; College of Medicine, Qatar University, Doha, Qatar.
⁴ The University of Queensland, Centre for Advanced Imaging, Brisbane, QLD, Australia.
⁵ Department of Environmental Health Sciences, University Medical Centre Freiburg, Freiburg, Germany.
⁶ Aquesta Pathology, Brisbane, QLD, Australia.
⁷ Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
⁸ Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
⁹ The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; Edith Cowan University, Joondalup, Western Australia, Australia.

Abstract

Background: Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers.

Methods: Male patients referred for elevated serum PSA or abnormal digital rectal examination provided ejaculate and PEUW samples. PSA, PCA3, and β2-microglobulin (β2M) were quantified in ejaculate and PEUW and compared with absolute and clinically significant (according to D'Amico criteria) PCa presence, as determined by biopsies. Diagnostic performance was determined and compared with serum PSA using receiver operating characteristic analysis.

Results: From 83 patients who provided PEUW samples, paired analysis with ejaculate samples was possible for 38 patients, while analysis in an unpaired, extended cohort was possible for 62 patients. PSA and PCA3 were detected in PEUW, normalized to β2M, and PCA3:PSA was calculated. In predicting absolute PCa status, PCA3:β2M in ejaculate [area under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA (AUC 0.617) with similar trends observed for the extended cohort. When considering clinically significant PCa presence, serum PSA in the comparison (AUC 0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: β2M (AUC 0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in the comparison (PCA3: β2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3: β2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was limited by sample size.

Conclusion: PEUW contains prostatic material, but has limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3-based markers in ejaculate are comparable to serum PSA and digital rectal examination-urine markers.

Keywords: Biomarker; Ejaculate; Prostate Cancer; Prostate Cancer Antigen 3; Prostate Specific Antigen; mRNA.