Lou Ning, Ruan An-Ming, Qiu Bin, Bao Lin, Xu Yu-Chen, Zhao Yan, Sun Ru-Lin, Zhang San-Tao, Xu Guang-Hua, Ruan Hai-Long, Yuan Chang-Fei, Han Wei-Wei, Shi Hang-Chuan, Yang Hong-Mei, Zhang Xiao-Ping
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan 430022, China.
Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, 13 HangKong Road, Wuhan 430030, China.
Urol Oncol. 2017 Jan;35(1):36.e7-36.e14. doi: 10.1016/j.urolonc.2016.07.012. Epub 2016 Sep 12.
Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal subtype of renal cell carcinoma, whose most effective measure of curing remains diagnosis and nephrectomy in its early phase. However, there is no feasible and recognized plasma biomarker for the clinical diagnosis of ccRCC. The objective of this study is to identify a novel plasma microRNA (miRNA) acting as an efficient diagnostic plasma biomarker in ccRCC.
The plasma miRNA expression profile was quantified by miRNA microarray. Validation of miRNA levels of plasmas and tissues were performed by quantitative reverse transcription polymerase chain reaction in 106 ccRCC, 28 renal angiomyolipomas (AML), and 123 healthy control plasmas and in 110 ccRCC tissues.
We found that plasma miR-144-3p levels in 106 ccRCC plasmas were remarkably up-regulated compared with that in healthy individuals and in patients with AML. miR-144-3p served as a promising plasma biomarker for yielding an area under the receiver operating characteristic curve of 0.91 with 87.10% sensitivity and 83.02% specificity in discriminating ccRCC from healthy individuals, and an area under the curve of 0.82 with 75.00% sensitivity and 71.70% specificity in discriminating ccRCC from patients with AML. In addition, plasma miR-144-3p levels were significantly decreased after surgery in 106 patients with ccRCC. Next, we examined miR-144-3p levels in 110 human ccRCC tissues, and found that miR-144-3p levels in ccRCC tissues were increased compared with adjacent normal tissues. Pearson correlation analysis revealed that miR-144-3p levels in tumor tissues were positively correlated with preoperative plasma miR-144-3p levels in the matched samples from patients with ccRCC. In addition, the miR-144-3p levels in ccRCC plasmas and tissues were increased in patients with advanced pT stage.
Our data indicate that miR-144-3p, which is significantly up-regulated in ccRCC plasmas and tissues, particularly with advanced pT stage, is a novel and excellent plasma biomarker for the diagnosis of ccRCC.
透明细胞肾细胞癌(ccRCC)是肾细胞癌中最常见且致死率最高的亚型,其最有效的治疗措施仍是早期诊断及肾切除术。然而,目前尚无可行且被认可的用于ccRCC临床诊断的血浆生物标志物。本研究的目的是鉴定一种新型血浆微小RNA(miRNA),作为ccRCC高效的诊断性血浆生物标志物。
采用miRNA微阵列对血浆miRNA表达谱进行定量分析。通过定量逆转录聚合酶链反应对106例ccRCC患者、28例肾血管平滑肌脂肪瘤(AML)患者及123例健康对照者的血浆以及110例ccRCC组织中的miRNA水平进行验证。
我们发现,106例ccRCC患者血浆中的miR-144-3p水平相较于健康个体及AML患者显著上调。miR-144-3p作为一种有前景的血浆生物标志物,在区分ccRCC与健康个体时,受试者工作特征曲线下面积为0.91,敏感性为87.10%,特异性为83.02%;在区分ccRCC与AML患者时,曲线下面积为0.82,敏感性为75.00%,特异性为71.70%。此外,106例ccRCC患者术后血浆miR-144-3p水平显著降低。接下来,我们检测了110例人ccRCC组织中的miR-144-3p水平,发现ccRCC组织中的miR-144-3p水平相较于相邻正常组织升高。Pearson相关性分析显示,肿瘤组织中的miR-144-3p水平与ccRCC患者匹配样本中术前血浆miR-144-3p水平呈正相关。此外,ccRCC患者血浆和组织中的miR-144-3p水平在pT分期较晚的患者中升高。
我们的数据表明,miR-144-3p在ccRCC血浆和组织中显著上调,尤其是在pT分期较晚的患者中,是一种用于诊断ccRCC的新型且优秀的血浆生物标志物。