Urinary transcript quantitation of CK20 and IGF2 for the non-invasive bladder cancer detection.

Abstract

PURPOSE:

Cytokeratin 20 (CK20) and insulin-like growth factor 2 (IGF2) were previously proposed to be elevated in clinical samples from patients with bladder cancer (BCa). A two cohort design validation study was used to assess the relevance for BCa detection by transcript quantitation of both markers in urine samples. Their diagnostic value was assessed in comparison with voided urine cytology (VUC).

METHODS:

RNA isolation was carried out using cellular sediments of urine samples from 196/103 histologically positive BCa patients, as well as 97/50 control subjects for the test (TC) and validation cohort (VC), respectively. Urinary transcript levels of CK20 and IGF2 were determined by qPCR.

RESULTS:

Relative transcript levels were significantly elevated 3.4/11-fold for CK20 and 188/64-fold for IGF2 (p < 0.001) in urine sediments of BCa patients compared to controls in the TC and VC, respectively. In a combined analysis, the resulting sensitivity (SN) (SNTC: 77.9; SNVC: 90.3%) and specificity (SP) (SPTC: 88.0; SPVC: 84.0%) were similar to that of VUC. The sensitivity of VUC in combination with CK20 and IGF2 was considerably increased (SNTC: 94.6; SNVC: 93.2%) while specificity was reduced (SPTC: 72.0; SPVC: 82.0%) compared to VUC alone in the test and validation cohort.

CONCLUSIONS:

Transcript levels of IGF2 and CK20 enabled the detection of BCa with a diagnostic performance similar to VUC. Combined analysis of voided urine cytology together with altered transcript levels of CK20 and IGF2 enhanced sensitivity, but did not improve overall test performance.

• Authors: Karsten Salomo, Doreen Huebner, Manja U Boehme, Alexander Herr, Werner Brabetz, Ulrike Heberling, Oliver W Hakenberg, Daniela Jahn, Marc-Oliver Grimm, Daniel Steinbach, Marcus Horstmann, Michael Froehner, Manfred P Wirth, Susanne Fuessel
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 143 Issue 9 Pg. 1757-1769 (Sep 2017) ISSN: 1432-1335 [Electronic] Germany
• PMID: 28484844 (Publication Type: Clinical Trial, Journal Article, Validation Study)

Chemical References

• Biomarkers, Tumor
• IGF2 protein, human
• KRT20 protein, human
• Keratin-20
• Insulin-Like Growth Factor II

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (urine)
• Carcinoma, Transitional Cell (diagnosis, urine)
• Cohort Studies
• Female
• Humans
• Insulin-Like Growth Factor II (urine)
• Keratin-20 (urine)
• Male
• Middle Aged
• Sensitivity and Specificity
• Urinary Bladder Neoplasms (diagnosis, urine)