Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience
Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience
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DOI：
10.1515/cclm.2007.133
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发表时间：
2007-01-01
影响因子：
6.8
通讯作者：
Orlando, Claudio
中科院分区：
文献类型：
--
作者：
Gelmini, Stefania;Quattrone, Silvia;Orlando, Claudio
背景：端粒酶-1(Tankyrase-1，TNKS-1)是聚腺苷二磷酸核糖聚合酶(PARP)家族中的一员，是人类端粒复合体的组成部分。PARPS以NAD(+)为底物，催化在蛋白质受体上形成长链多聚ADP-核糖。TNKS-1与端粒DNA结合蛋白TTAGGG重复结合因子1(TRF1)相互作用，TRF1是端粒长度的负调控因子。TNKS-1是端粒延长的正性调节因子，其活性在某些人类肿瘤中出现上调。方法：采用实时定量RT-PCR方法首次检测了膀胱移行细胞癌(TCC)患者肿瘤组织、配对正常粘膜和尿沉渣中TNKS-1mRNA的表达。样本来自41例连续患者，20例非肌肉侵袭性(PTA-PT1)和21例肌肉侵袭性(>；=pt2)膀胱TCC。结果：PTA-PT1肿瘤组织中TnKS-1mRNA的表达水平显著高于PT2患者(p<；0.0001)。在TCC患者尿沉渣中，TNKS-1mRNA水平显著高于健康对照组，与肿瘤分期无关，其中以<gt；=pt2患者最高。其中31例患者尿TNKS-1mRNA水平升高，对PTA-PT1和>；=pt2肿瘤的敏感性分别为81%和65%。在PTA-PT1肿瘤患者中，有11例在初次电切后18个月内复发。结论：在本研究中，膀胱移行细胞癌患者尿沉渣中的TNKS-1mRNA水平与肿瘤分期有关，术前水平越高，早期复发风险越高。
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.