title: A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer.
abstract: Although prostate-specific antigen (PSA) serum level is currently the standard of care for prostate cancer screening in the United States, it lacks ideal specificity and additional biomarkers are needed to supplement or potentially replace serum PSA testing. Emerging evidence suggests that monitoring the noncoding RNA transcript PCA3 in urine may be useful in detecting prostate cancer in patients with elevated PSA levels. Here, we show that a multiplex panel of urine transcripts outperforms PCA3 transcript alone for the detection of prostate cancer. We measured the expression of seven putative prostate cancer biomarkers, including PCA3, in sedimented urine using quantitative PCR on a cohort of 234 patients presenting for biopsy or radical prostatectomy. By univariate analysis, we found that increased GOLPH2, SPINK1, and PCA3 transcript expression and TMPRSS2:ERG fusion status were significant predictors of prostate cancer. Multivariate regression analysis showed that a multiplexed model, including these biomarkers, outperformed serum PSA or PCA3 alone in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.758 for the multiplexed model versus 0.662 for PCA3 alone (P = 0.003). The sensitivity and specificity for the multiplexed model were 65.9% and 76.0%, respectively, and the positive and negative predictive values were 79.8% and 60.8%, respectively. Taken together, these results provide the framework for the development of highly optimized, multiplex urine biomarker tests for more accurate detection of prostate cancer.
authors.affiliation: Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Laxman
authors.forename: David S
authors.initials: DS
authors.lastname: Morris
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yu
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lonigro
authors.forename: Alex
authors.initials: A
authors.lastname: Tsodikov
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000652:urine; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D002352:Carrier Proteins / Q000235:genetics / Q000652:urine; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000652:urine; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000652:urine*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000652:urine; D010455:Peptides / Q000235:genetics / Q000652:urine; D016133:Polymerase Chain Reaction / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics / Q000652:urine*; D012334:RNA, Neoplasm / Q000235:genetics; D019998:Racemases and Epimerases / Q000235:genetics / Q000652:urine; D015534:Trans-Activators / Q000235:genetics / Q000652:urine; D000071230:Transcriptional Regulator ERG; D000071165:Trefoil Factor-3; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C072312:ERG protein, human; C410824:GOLM1 protein, human; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D010455:Peptides; D012334:RNA, Neoplasm; C486642:SPINK1 protein, human; C082495:TFF3 protein, human; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D000071165:Trefoil Factor-3; C479341:prostate cancer antigen 3, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase