Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma

Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma
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DOI:
10.1158/1078-0432.ccr-06-0134
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发表时间:
2006-08-15
影响因子:
11.5
通讯作者:
Chen, Wei-Feng
Chen, Wei-Feng
中科院分区:
医学1区
文献类型:
--
作者:
Wang, Xiao-Song;Zhang, Zheng;Chen, Wei-Feng

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目的:膀胱移行细胞癌是我国泌尿生殖系统最常见的恶性肿瘤.早期诊断新的和复发的膀胱癌,然后及时治疗,将有助于降低死亡率。目前临床上还没有令人满意的膀胱癌标志物。实验设计:本研究采用了综合表达序列标签分析、基因表达系列分析和微阵列分析等方法,快速发现了尿路上皮癌相关基因1(UCA 1)。UCA 1基因的特点和其作为尿液标记物的性能进行了分析,通过逆转录-PCR与尿沉渣。共212人被纳入这项研究,94人膀胱癌,33输尿管/盆腔癌,和85个正常和其他尿路疾病controls.Results:UCA 1被确定为一个新的非编码RNA基因显着上调TCC,它是最TCC特异性基因尚未确定。其cDNA全长为1,439 bp,序列分析表明其属于人内源性逆转录病毒H家族。临床试验表明,UCA_1检测对膀胱癌的诊断具有高度特异性(91.8%,78/85)和高度敏感性(80.9%,76/94),特别是对浅表性G2-G3患者有价值(91.1%,41/45)。结论:UCA 1是一种敏感性高、特异性强的膀胱癌特异性标志物。这可能对术后无创随访具有重要意义。这项研究还强调了通过将计算机分离方法与基于RNA检测方案的转化临床测试相结合来实现新的癌症诊断检测的捷径。
Purpose: The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded.Experimental Design: In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls.Results: UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC.Conclusions: UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.