Cancer Research Institute, M.D. Anderson Cancer Center Orlando, Orlando, FL, USA.
Cancer Epidemiol Biomarkers Prev. 2012 Dec;21(12):2149-58. doi: 10.1158/1055-9965.EPI-12-0428. Epub 2012 Oct 24.
Bladder cancer is among the five most common malignancies worldwide, and due to high rates of recurrence, one of the most prevalent. Improvements in noninvasive urine-based assays to detect bladder cancer would benefit both patients and health care systems. In this study, the goal was to identify urothelial cell transcriptomic signatures associated with bladder cancer.
Gene expression profiling (Affymetrix U133 Plus 2.0 arrays) was applied to exfoliated urothelia obtained from a cohort of 92 subjects with known bladder disease status. Computational analyses identified candidate biomarkers of bladder cancer and an optimal predictive model was derived. Selected targets from the profiling analyses were monitored in an independent cohort of 81 subjects using quantitative real-time PCR (RT-PCR).
Transcriptome profiling data analysis identified 52 genes associated with bladder cancer (P ≤ 0.001) and gene models that optimally predicted class label were derived. RT-PCR analysis of 48 selected targets in an independent cohort identified a 14-gene diagnostic signature that predicted the presence of bladder cancer with high accuracy.
Exfoliated urothelia sampling provides a robust analyte for the evaluation of patients with suspected bladder cancer. The refinement and validation of the multigene urothelial cell signatures identified in this preliminary study may lead to accurate, noninvasive assays for the detection of bladder cancer.
The development of an accurate, noninvasive bladder cancer detection assay would benefit both the patient and health care systems through better detection, monitoring, and control of disease.
膀胱癌是全球最常见的五种恶性肿瘤之一,由于其高复发率,也是最常见的肿瘤之一。提高非侵入性尿液检测膀胱癌的方法将使患者和医疗保健系统受益。在这项研究中,我们的目标是确定与膀胱癌相关的尿路上皮细胞转录组特征。
应用基因表达谱(Affymetrix U133 Plus 2.0 阵列)对 92 例已知膀胱疾病状态的受试者的脱落尿路上皮进行分析。计算分析确定了膀胱癌的候选生物标志物,并得出了最佳预测模型。使用定量实时 PCR(RT-PCR)在 81 例独立队列中监测分析中的选定靶标。
转录组分析确定了 52 个与膀胱癌相关的基因(P ≤ 0.001),并得出了最佳预测类标签的基因模型。在独立队列中对 48 个选定靶标的 RT-PCR 分析确定了一个 14 基因诊断特征,可准确预测膀胱癌的存在。
脱落尿路上皮采样为疑似膀胱癌患者的评估提供了一个可靠的分析物。在这项初步研究中确定的多基因尿路上皮细胞特征的改进和验证可能会导致用于膀胱癌检测的准确、非侵入性检测方法。
开发准确、非侵入性的膀胱癌检测方法将通过更好地检测、监测和控制疾病,使患者和医疗保健系统受益。