Unoki M, Kelly J D, Neal D E, Ponder B A J, Nakamura Y, Hamamoto R
Laboratory for Biomarker Development, The Institute of Physical and Chemical Research, RIKEN, Tokyo, Japan.
Br J Cancer. 2009 Jul 7;101(1):98-105. doi: 10.1038/sj.bjc.6605123. Epub 2009 Jun 2.
Bladder cancer is the second most common cancer of the urinary system. Early diagnosis of this tumour and estimation of risk of future progression after initial transuretherial resection have a significant impact on prognosis. Although there are several molecular markers for the diagnosis and prognosis for this tumour, their accuracy is not ideal. Previous reports have shown that UHRF1 (ubiquitin-like with PHD and ring-finger domains 1) is essential for cellular proliferation. In this study, we examined whether UHRF1 can be a novel molecular marker of bladder cancer.
We performed real-time TaqMan quantitative reverse transcription-PCR and immunohistochemistry to examine expression levels of UHRF1 in bladder and kidney cancers.
Significant overexpression of UHRF1 was observed in bladder cancer. The overexpression was correlated with the stage and grade of the cancer. Although UHRF1 expression in muscle-invasive cancer was greater than in non-invasive (pTa) or superficially invasive (pT1) cancers, UHRF1 could still be detected by immunohistochemistry in these early-stage cancers. Overexpression of UHRF1 in bladder cancer was associated with increased risk of progression after transurethral resection. High expression of UHRF1 in kidney cancer was also observed. But the increased levels of UHRF1 in kidney cancer were less significant compared with those in bladder cancer.
Our result indicates that an immunohistochemistry-based UHRF1 detection in urine sediment or surgical specimens can be a sensitive and cancer-specific diagnostic and/or prognosis method, and may greatly improve the current diagnosis based on cytology.
膀胱癌是泌尿系统第二常见的癌症。该肿瘤的早期诊断以及初次经尿道切除术后未来进展风险的评估对预后有重大影响。尽管有几种用于该肿瘤诊断和预后的分子标志物,但其准确性并不理想。先前的报道表明,UHRF1(含PHD和环指结构域的泛素样蛋白1)对细胞增殖至关重要。在本研究中,我们检测了UHRF1是否可成为膀胱癌的一种新型分子标志物。
我们进行了实时TaqMan定量逆转录PCR和免疫组化,以检测UHRF1在膀胱癌和肾癌中的表达水平。
在膀胱癌中观察到UHRF1显著过表达。这种过表达与癌症的分期和分级相关。尽管肌肉浸润性癌中UHRF1的表达高于非浸润性(pTa)或浅表浸润性(pT1)癌,但在这些早期癌症中仍可通过免疫组化检测到UHRF1。膀胱癌中UHRF1的过表达与经尿道切除术后进展风险增加相关。在肾癌中也观察到UHRF1高表达。但与膀胱癌相比,肾癌中UHRF1水平升高的程度较小。
我们的结果表明,基于免疫组化在尿沉渣或手术标本中检测UHRF1可以是一种敏感且癌症特异性的诊断和/或预后方法,并且可能极大地改善当前基于细胞学的诊断。