Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience (original) (raw)

Abstract

Background: The enzyme tankyrase-1 (TNKS-1), a member of the growing family of poly(ADP-ribose) polymerases (PARPs), was identified as a component of the human telomeric complex. PARPs catalyze the formation of long chains of poly(ADP-ribose) onto protein acceptors using NAD+ as a substrate. TNKS-1 interacts with the telomeric DNA-binding protein TTAGGG repeat-binding factor 1 (TRF1), which is a negative regulator of telomere length. TNKS-1 is a positive regulator of telomere elongation and its activity appears to be upregulated in some human cancers.

Methods: We evaluated for the first time TNKS-1 mRNA expression by real time RT-PCR in tumor tissue, paired normal mucosa and urine sediment in patients with transitional cell carcinoma (TCC) of the bladder. Samples were collected from 41 consecutive patients, 20 with non-muscle-invasive (pTa-pT1) and 21 with muscle-invasive (≥pT2) bladder TCC. Results obtained in urine sediment were compared with those from 40 healthy subjects matched for age and sex.

Results: In pTa-pT1 tumor tissues, TNKS-1 mRNA levels were significantly higher than in ≥pT2 patients (p<0.0001). In urine sediment from TCC patients, independent of tumor stage, TNKS-1 mRNA levels were significantly higher than in healthy controls, with maximal levels in ≥pT2 patients. In particular, TNKS-1 mRNA levels in urine were elevated in 31/41 patients with a sensitivity of 81% in ≥pT2 tumors and 65% in pTa-pT1 TCC. Of patients with pTa-pT1 tumors, 11 had a recurrence within 18 months after initial transurethral resection. In these patients, urine levels of TNKS-1 mRNA were higher than in non-relapsing patients (p=0.038).

Conclusions: In this preliminary study, TNKS-1 mRNA in urine sediment from patients with bladder TCC correlated with tumor stage, and higher preoperative levels were associated with increased risk of early recurrence.

Clin Chem Lab Med 2007;45:862–6.

Corresponding author: Prof. Claudio Orlando, Clinical Biochemistry Unit, Department of Clinical Physiopathology, University of Florence, viale Pieraccini 6, 50139 Florence, Italy Phone: +39-055-4271440, Fax: +39-055-4271413 c.orlando@dfc.unifi.it

Received: 2006-11-16

Accepted: 2007-3-5

Published Online: 2007-07-08

Published in Print: 2007-07-01