Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience.
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.
Gelmini
Stefania
S
Clinical Biochemistry Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
Quattrone
Silvia
S
Malentacchi
Francesca
F
Villari
Donata
D
Travaglini
Fabrizio
F
Giannarini
Gianluca
G
Della Melina
Alessandro
A
Pazzagli
Mario
M
Nicita
Giulio
G
Selli
Cesare
C
Orlando
Claudio
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D038501:Tankyrases / Q000235:genetics* / Q000378:metabolism; D016615:Telomere; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D038501:Tankyrases