Diagnostic and prognostic value of bladder cancer-related transcript markers in urine

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Juliane Schmidt - , Department of Urology (Author)
  • Catharina Propping - , Department of Urology (Author)
  • Woei Yun Siow - , Raffles Hospital (Author)
  • Andrea Lohse-Fischer - , Department of Urology (Author)
  • Marieta Toma - , Institute of Pathology (Author)
  • Anka Baldauf-Twelker - , Department of Urology (Author)
  • Oliver W. Hakenberg - , University of Rostock (Author)
  • Manfred P. Wirth - , Department of Urology (Author)
  • Susanne Fuessel - , Department of Urology (Author)

Abstract

Purpose: Since cytology as the current “gold standard” for noninvasive detection of bladder cancer (BCa) is characterized by a relatively low sensitivity, urinary transcript levels of survivin (SVV), Ki-67 and cytokeratin 20 (CK20) were evaluated as alternative or complementary biomarkers. Furthermore, their prognostic value was investigated. Methods: Voided urine samples from 105 BCa patients and 156 controls were included. Total RNA was isolated from urine pellets and reverse-transcribed into cDNA. Expression levels of SVV, Ki-67 and CK20 were determined by quantitative PCR and normalized to the housekeeping gene TBP. Diagnostic performance of transcript markers and cytology was assessed by receiver operating characteristic (ROC) curve analyses. The prognostic value of the transcript markers was calculated by Cox proportional hazards models. Results: ROC analyses resulted in AUC values between 0.71 (Ki-67) and 0.86 (CK20), indicating an appropriate diagnostic power. Using specifically defined cutoff values, the expression levels of the assessed biomarkers were significantly higher in urine specimens from BCa patients compared to control group (Mann–Whitney U test p < 0.001). Specificity ranged from 75 % (SVV) to 84 % (CK20) and sensitivity from 56 % (Ki-67) to 87 % (CK20). In combination with cytology, the sensitivity increased up to 97 % (CK20). With regard to prognostic power, only SVV showed a significant, but not independent impact on the risk of recurrence (p = 0.008). Conclusions: Quantitative assessment of tumor-related transcript markers, particularly of CK20, may serve as a noninvasive method to identify patients with BCa. Moreover, SVV appears to be useful as a marker for a high risk of recurrence.

Details

Original languageEnglish
Pages (from-to)401-414
Number of pages14
JournalJournal of cancer research and clinical oncology
Volume142
Issue number2
Publication statusPublished - 1 Feb 2016
Peer-reviewedYes

External IDs

PubMed 26328914

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • BIRC5, CK20, Ki-67, Survivin, Urine, Urothelial carcinoma