title: Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers.
abstract: We explore noninvasive clinical applications of multiple disease-specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate-specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy-positive cases from 92 patients (42.4%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high-grade cancer, with a predictive accuracy of 80% when coupled with PSA density. The individualized risk scores further stratified a high-risk group that is composed of 92% high-grade cancers and a low-risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis.
authors.affiliation: Division of Urology, Department of Surgery, Research Institute of the McGill University Health Center Montreal, Quebec, Canada, H3G 1A4.
authors.forename: Sam W
authors.initials: SW
authors.lastname: Chan
authors.forename: Phuong-Nam
authors.initials: PN
authors.lastname: Nguyen
authors.forename: Philippe
authors.initials: P
authors.lastname: Violette
authors.forename: Fadi
authors.initials: F
authors.lastname: Brimo
authors.forename: Yosh
authors.initials: Y
authors.lastname: Taguchi
authors.forename: Armen
authors.initials: A
authors.lastname: Aprikian
authors.forename: Junjian Z
authors.initials: JZ
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics* / Q000652:urine; D001707:Biopsy, Needle; D042241:Early Diagnosis; D020869:Gene Expression Profiling / Q000379:methods; D052138:Genes, Neoplasm; D005819:Genetic Markers; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D015514:Oncogene Proteins, Fusion; C529660:TMPRSS2-ETS fusion protein, human; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Biopsy cohort; ETS fusions; TMPRSS2; diagnosis and prognosis; prostate cancer; urine test