Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder
Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder
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DOI：
10.1158/1078-0432.ccr-07-1672
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发表时间：
2008-02-01
影响因子：
11.5
通讯作者：
Guilford, Parry
中科院分区：
文献类型：
--
作者：
Holyoake, Andrew;O'Sullivan, Paul;Guilford, Parry
目的：新的标志物，使膀胱移行细胞癌（TCC）的百分比，在膀胱肌层的入侵之前被诊断为增加，将降低与这种疾病相关的发病率和死亡率。本研究的目的是开发一种基于mRNA标记和简单基因特征的简单、准确的尿液检测，其（a）可以在肌肉侵入之前检测TCC，同时在血尿或尿路感染患者中保持高特异性，并且（B）鉴定最可能患有3级或>= T1期疾病的患者。使用来自75名TCC患者和77名患有其他泌尿系统疾病的对照患者的2 mL排尿，通过定量逆转录-PCR来表征在Ta期肿瘤和/或T1至T4期肿瘤中高过表达但在血液或炎性细胞中低表达的RNA标志物。RNA CDC 2、MOK、IGFBP 5和HOXA 13的组合分别检测了48%、90%和100%的Ta、T1和> T1期TCC，特异性为85%。对于原发性（非复发性）Ta肿瘤，Ta肿瘤的检测增加到60%，对于直径>= 1 cm的Ta肿瘤，Ta肿瘤的检测增加到76%。20名尿路感染对照患者的检测特异性为80%。CDC 2和HOXA 13联合检测可区分1 ~ 2级膀胱移行细胞癌和3级或≥ T1期膀胱移行细胞癌，特异性和敏感性接近80%。结论：尿基因表达特征可作为膀胱癌的准确检测和定性的尿标志物。
Purpose: New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on m RNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage >= T1 disease.Experimental Design: RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases.Results: A combination of the RNAs CDC2, MOK, IGFBP5, and HOXA13 detected 48%,90%, and 100% of stage Ta,T1, and > T1 TCCs, respectively, at a specificity of 85%. Detection of Ta tumors increased to 60% for primary (non-recurrent) Ta tumors and 76% for Ta tumors >= 1 cm in diameter. Test specificity was 80% for the 20 control patients with urinary tract infections. The combination of CDC2 and HOXA13 distinguished between grade 1 to 2 TCCs and grade 3 or stage >= T1 TCCs with similar to 80% specificity and sensitivity.Conclusions: Simple gene expression signatures can be used as urine markers for the accurate detection and characterization of bladder cancer.