Clinical utility of a novel urine-based gene fusion TTTY15-USP9Y in predicting prostate biopsy outcome

Urol Oncol. 2015 Sep;33(9):384.e9-20. doi: 10.1016/j.urolonc.2015.01.019. Epub 2015 May 23.

Abstract

Objective: In recent years, great effort has been made to explore new biomarkers for early detection of prostate cancer. Our previous study has demonstrated the high prevalence of TTTY15-USP9Y in prostate cancer samples from a Chinese population. Our aim was to evaluate the clinical utility of TTTY15-USP9Y in predicting the prostate biopsy outcome.

Materials and methods: We retrospectively examined the expression of TTTY15-USP9Y in 226 qualified urine sediment samples. Total RNA was extracted from the urine sediment by using TRIzol reagent, and complementary DNA was synthesized using TransPlex Complete Whole Transcriptome Amplification Kit (WTA2). Real-time quantitative polymerase chain reaction was performed to evaluate the expression of TTTY15-USP9Y and the prostate cancer-specific antigen (PSA) level. The TTTY15-USP9Y score was calculated as 2(Ct(PSA)-Ct(TTTY15-USP9Y))× 1,000.

Results: The TTTY15-USP9Y score was statistically significantly higher in men with positive biopsy outcome than in men with negative biopsy outcome (P<0.001). The area under the curve was 0.828 for the TTTY15-USP9Y score in the entire patient cohort. The TTTY15-USP9Y score׳s cutoff of 90.28 provided the optimal balance between sensitivity (84.0%) and specificity (77.5%). The combination of PSA level and the TTTY15-USP9Y score significantly improved the diagnostic performance of PSA level (P = 0.001). The TTTY15-USP9Y score alone was superior to PSA level, percent free PSA, and PSA density (serum PSA/prostate volume) in the subgroup of clinical interest (PSA level: 4-10ng/ml, gray zone). Univariable and multivariable logistic analyses indicated that TTTY15-USP9Y score, PSA level, age, and prostate volume were independent predictors of PCa. Adding the TTTY15-USP9Y score in the clinical base model (PSA level, age, and prostate volume) could bring a higher net benefit and reduce more unnecessary biopsies in the defined range of interest (10%-40% threshold probability).

Conclusion: In conclusion, our study explored the potential utility of measuring the TTTY15-USP9Y score in post-digital rectal examination urine samples to predict biopsy outcome and provided the basis for the utility of this novel gene fusion in multicenter and large cohort studies.

Keywords: TTTY15-USP9Y; biomarker; gene fusion; prostate cancer; urine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Area Under Curve
  • Asian People
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / urine
  • Biopsy
  • Humans
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / urine
  • Prognosis
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / urine
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Sensitivity and Specificity
  • Ubiquitin Thiolesterase / genetics*
  • Ubiquitin Thiolesterase / urine

Substances

  • Biomarkers, Tumor
  • Minor Histocompatibility Antigens
  • Oncogene Proteins, Fusion
  • USP9Y protein, human
  • Ubiquitin Thiolesterase