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


METHODS
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.
Wang
Xiao-Song
XS
Department of Urology, First Hospital of Peking University, Institute of Urology, Peking University, Beijing, China.
Zhang
Zheng
Z
Wang
Hong-Cheng
HC
Cai
Jian-Liang
JL
Xu
Qing-Wen
QW
Li
Meng-Qiang
MQ
Chen
Yi-Cheng
YC
Qian
Xiao-Ping
XP
Lu
Tian-Jing
TJ
Yu
Li-Zhang
LZ
Zhang
Yu
Y
Xin
Dian-Qi
DQ
Na
Yan-Qun
YQ
Chen
Wei-Feng
WF
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000652:urine; D002874:Chromosome Mapping / Q000379:methods; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000652:urine; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000652:urine
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D005819:Genetic Markers; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C515159:UCA1 RNA, human