Salomo Karsten, Huebner Doreen, Boehme Manja U, Herr Alexander, Brabetz Werner, Heberling Ulrike, Hakenberg Oliver W, Jahn Daniela, Grimm Marc-Oliver, Steinbach Daniel, Horstmann Marcus, Froehner Michael, Wirth Manfred P, Fuessel Susanne
Department of Urology, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
Biotype Diagnostic GmbH, Dresden, Germany.
J Cancer Res Clin Oncol. 2017 Sep;143(9):1757-1769. doi: 10.1007/s00432-017-2433-3. Epub 2017 May 8.
Cytokeratin 20 (CK20) and insulin-like growth factor 2 (IGF2) were previously proposed to be elevated in clinical samples from patients with bladder cancer (BCa). A two cohort design validation study was used to assess the relevance for BCa detection by transcript quantitation of both markers in urine samples. Their diagnostic value was assessed in comparison with voided urine cytology (VUC).
RNA isolation was carried out using cellular sediments of urine samples from 196/103 histologically positive BCa patients, as well as 97/50 control subjects for the test (TC) and validation cohort (VC), respectively. Urinary transcript levels of CK20 and IGF2 were determined by qPCR.
Relative transcript levels were significantly elevated 3.4/11-fold for CK20 and 188/64-fold for IGF2 (p < 0.001) in urine sediments of BCa patients compared to controls in the TC and VC, respectively. In a combined analysis, the resulting sensitivity (SN) (SN: 77.9; SN: 90.3%) and specificity (SP) (SP: 88.0; SP: 84.0%) were similar to that of VUC. The sensitivity of VUC in combination with CK20 and IGF2 was considerably increased (SN: 94.6; SN: 93.2%) while specificity was reduced (SP: 72.0; SP: 82.0%) compared to VUC alone in the test and validation cohort.
Transcript levels of IGF2 and CK20 enabled the detection of BCa with a diagnostic performance similar to VUC. Combined analysis of voided urine cytology together with altered transcript levels of CK20 and IGF2 enhanced sensitivity, but did not improve overall test performance.
细胞角蛋白20（CK20）和胰岛素样生长因子2（IGF2）先前被认为在膀胱癌（BCa）患者的临床样本中升高。采用双队列设计验证研究，通过对尿液样本中这两种标志物的转录本定量来评估其与BCa检测的相关性。与尿脱落细胞学检查（VUC）相比，评估了它们的诊断价值。
分别使用来自196/103例组织学确诊的BCa患者以及97/50例对照受试者的尿液样本细胞沉淀物进行RNA分离，用于测试队列（TC）和验证队列（VC）。通过qPCR测定CK20和IGF2的尿液转录水平。
与TC和VC中的对照相比，BCa患者尿液沉淀物中CK20的相对转录水平分别显著升高3.4/11倍，IGF2的相对转录水平分别显著升高188/64倍（p < 0.001）。在联合分析中，所得敏感性（SN）（SN：77.9；SN：90.3%）和特异性（SP）（SP：88.0；SP：84.0%）与VUC相似。与单独的VUC相比，在测试队列和验证队列中，VUC与CK20和IGF2联合使用时敏感性显著提高（SN：94.6；SN：93.2%），而特异性降低（SP：72.0；SP：82.0%）。
IGF2和CK20的转录水平能够检测BCa，其诊断性能与VUC相似。尿脱落细胞学检查与CK20和IGF2转录水平改变的联合分析提高了敏感性，但未改善整体检测性能。
