切换至 "中华医学电子期刊资源库"

中华临床实验室管理电子杂志 ›› 2018, Vol. 06 ›› Issue (02) : 84 -88. doi: 10.3877/cma.j.issn.2095-5820.2018.02.005

所属专题: 文献

实验研究

肾细胞癌患者血清外泌体miR-181a-3p表达水平的临床价值
王成1,(), 田亚萍1, 丁梦1, 张翠平1, 汪俊军1, 张春妮1,()   
  1. 1. 210002 解放军南京军区南京总医院临床检验科
  • 收稿日期:2018-04-02 出版日期:2018-05-28
  • 通信作者: 王成, 张春妮
  • 基金资助:
    国家自然科学基金项目(81772282); 江苏省"科教强卫工程"青年医学人才项目(QNRC2016893)

The clinical value of serum exosomal miR-181a-3p levels in patients with renal cell carcinoma

Cheng Wang1,(), Yaping Tian1, Meng Ding1, Cuiping Zhang1, Junjun Wang1, Chunni Zhang1,()   

  1. 1. Department of Clinical Laboratory, the PLA Nanjing General Hospital of Nanjing Military Region, Nanjing 210002, China
  • Received:2018-04-02 Published:2018-05-28
  • Corresponding author: Cheng Wang, Chunni Zhang
  • About author:
    Corresponding author: Wang Cheng, Email: ;
    Zhang Chunni, Email:
引用本文:

王成, 田亚萍, 丁梦, 张翠平, 汪俊军, 张春妮. 肾细胞癌患者血清外泌体miR-181a-3p表达水平的临床价值[J/OL]. 中华临床实验室管理电子杂志, 2018, 06(02): 84-88.

Cheng Wang, Yaping Tian, Meng Ding, Cuiping Zhang, Junjun Wang, Chunni Zhang. The clinical value of serum exosomal miR-181a-3p levels in patients with renal cell carcinoma[J/OL]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2018, 06(02): 84-88.

目的

探讨肾细胞癌(renal cell carcinoma,RCC)患者血清外泌体微小核糖核酸-181a-3p(microRNA-181a-3p, miR-181a-3p)的表达变化,及其作为非侵入性辅助诊断RCC标志的临床价值。

方法

收集2016年6月至2017年6月期间,南京总医院泌尿外科收治的未经治疗的79例RCC患者和75名年龄、性别匹配的健康体检者血清标本,分离血清外泌体并提取RNA。用实时荧光定量聚合酶链反应(quantitative real-time polymerase chai reaction,qRT-PCR)检测两组miR-181a-3p水平的2-△Ct相对定量含量,并采用多种统计方法分析外泌体miR-181a-3p诊断RCC的效能。

结果

qRT-PCR检测RCC患者血清外泌体miR-181a-3p的表达水平为0.264(0.095~0.782),较健康对照组[0.068(0.032~0.130)]明显上调(U=1022,P<0.001);同时,血清外泌体miR-181a-3p水平在早期(I/II期)RCC患者[0.202(0.105~0.543)]中也显著升高(U=699,P<0.001)。血清外泌体miR-181a-3p的受试者工作特征曲线(receiver operating characteristic curve,ROC)区分RCC与健康对照者的曲线下面积(AUC)为0.828(95%CI:0.765~0.890),敏感度为72.2%,特异度为72.0%;诊断I/II期RCC患者的AUC为0.837(95%CI:0.771~0.902),敏感度和特异度分别为75.4%和72.0%。经逻辑回归分析,血清外泌体miR-181a-3p是RCC的独立危险因素(OR=6.662,95%CI:3.294~13.474,P<0.001)。

结论

RCC患者尤其早期患者血清外泌体miR-181a-3p显著升高,其可作为非侵入性辅助诊断RCC的新型分子标志。

Objective

To investigated the expression of serum exosomal microRNA-181a-3p (miR-181a-3p) in patients with renal cell carcinoma (RCC) and to evaluate its clinical value as a noninvasive diagnostic marker for RCC.

Methods

Seventy-nine RCC patients from Department of Urology and 75 age-sex matched healthy individuals from Health Checkup Center in Nanjing General Hospital between June 2016 and June 2017 were enrolled in this study. Serum exosome were isolated from the patients and healthy individuals, and the levels of exosomal miR-181a-3p were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The clinical value of serum exosomal miR-181a-3p were further assessed by receiver operating characteristic curve (ROC) and logistics analyses.

Results

The relative expression levels of serum exosomal miR-181a-3p in RCC patients [0.264 (0.095-0.782)] were significantly higher than those in healthy individuals [0.068 (0.032-0.130), U=1022, P<0.001]. Moreover, the levels of serum exosomal miR-181a-3p were also significantly higher in early stage RCC patients [0.202 (0.105-0.543)] than those in healthy individuals (U=699, P<0.001). Receive operating characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) for discriminating all RCC patients from healthy individuals was 0.828 (95%CI:0.765-0.890), and when at the optimal cutoff, the sensitivity was 72.2% and the specificity was 72.0%. The AUC for differentiating early stage RCC patients from healthy individuals was 0.837 (95%CI:0.771-0.902), with the sensitivity was 75.4% and the specificity was 72.0% when at the same cutoff. In addition, logistic regression analyses revealed that serum exosomal miR-181a-3p was an independent risk factor of RCC (odds ratio, OR=6.662, 95%CI:3.294-13.474, P<0.001).

Conclusion

Serum exosomal miR-181a-3p levels are significantly increased in RCC patients, especially the early patients, and may be served as a novel non-invasive auxiliary molecular diagnostic marker for RCC.

图1 血清外泌体miR-181a-3p诊断79例RCC患者(a)和57例早期RCC患者(b)的ROC曲线图
1
Capitanio U, Montorsi F. Renal cancer [J]. Lancet, 2016, 387(10021):894-906.
2
Golovastova MO, Korolev DO, Tsoy LV, et al. Biomarkers of Renal Tumors: the Current State and Clinical Perspectives [J]. Curr Urol Rep, 2017,18(1):3.
3
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function [J]. Cell, 2004,116(2):281-297.
4
Zhang Y, Liu D, Chen X, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration [J]. Mol Cell, 2010,39(1):133-144.
5
Bahrami A, Aledavood A, Anvari K, et al. The prognostic and therapeutic application of microRNAs in breast cancer: Tissue and circulating microRNAs [J]. J Cell Physiol, 2018,233(2):774-786.
6
Greither T, Vorwerk F, Kappler M, et al. Salivary miR-93 and miR-200a as post-radiotherapy biomarkers in head and neck squamous cell carcinoma [J]. Oncol Rep, 2017,38(2):1268-1275.
7
Wong TS, Liu XB, Wong BY, et al. Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue [J]. Clin Cancer Res, 2008,14(9):2588-2592.
8
Lei Z, Ma X, Li H, et al. Up-regulation of miR-181a in clear cell renal cell carcinoma is associated with lower KLF6 expression, enhanced cell proliferation, accelerated cell cycle transition, and diminished apoptosis [J]. Urol Oncol, 2018,36(3):93. e23-93. e37.
9
Boguslawska J, Sokol E, Rybicka B, et al. microRNAs target SRSF7 splicing factor to modulate the expression of osteopontin splice variants in renal cancer cells [J]. Gene, 2016,595(2):142-149.
10
Ge YZ, Xu LW, Zhou CC, et al. A BAP1 Mutation-specific MicroRNA Signature Predicts Clinical Outcomes in Clear Cell Renal Cell Carcinoma Patients with Wild-type BAP1 [J]. J Cancer, 2017, 8(13):2643-2652.
11
Wan S, Wang J, Wang J, et al. Increased serum miR-7 is a promising biomarker for type 2 diabetes mellitus and its microvascular complications [J]. Diabetes Res Clin Pract, 2017,130:171-179.
12
Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases [J]. Cell Res, 2008,18(10):997-1006.
13
van Niel G, D′Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles [J]. Nat Rev Mol Cell Biol, 2018,19(4):213-228.
14
MacLennan S, Imamura M, Lapitan MC, et al. Systematic review of perioperative and quality-of-life outcomes following surgical management of localised renal cancer [J]. Eur Urol, 2012,62(6):1097-117.
[1] 朱梅梅, 徐超丽, 田付丽, 王丹丹, 杨斌. 超声造影对Ⅰ型与Ⅱ型乳头状肾细胞癌的鉴别诊断[J/OL]. 中华医学超声杂志(电子版), 2021, 18(09): 868-874.
[2] 赵丽, 蔡瑞明, 赵纪强, 林民专, 陈志勇, 彭娟. 肾移植术后新发泌尿系统恶性肿瘤二例并文献复习[J/OL]. 中华移植杂志(电子版), 2024, 18(01): 35-39.
[3] 周慧宇, 吕定阳, 双卫兵. 联合系统性免疫炎症指数和预后营养指数预测腹腔镜肾切除术后肾癌患者的预后[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(03): 225-231.
[4] 黄兴, 王蕾, 夏丹. 靶向免疫治疗时代下减瘤性肾切除术在转移性肾细胞癌治疗中的价值[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(03): 208-213.
[5] 杨龙雨禾, 王跃强, 招云亮, 金溪, 卫娜, 杨智明, 张贵福. 人工智能辅助临床决策在泌尿系肿瘤的应用进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(02): 178-182.
[6] 邓新军, 李正明, 李文彬. 广东省医学会泌尿外科疑难病例多学科会诊(第14期)——左肾原发恶性肿瘤并发于肺癌并脑转移[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(01): 114-117.
[7] 加素尔·巴吐尔, 徐铭泽, 唐钵, 曾浩, 苏力坦·乌斯曼, 陈羽. 广东省医学会泌尿外科疑难病例多学科会诊(第14期)——左肾原发罕见恶性肿瘤并全身多处转移[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(01): 110-113.
[8] 张磊磊, 蒋方, 徐疾飞, 周真文, 郭志文, 毕满华. 乳头状肾细胞癌预后预测模型的构建及验证[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 343-350.
[9] 周硕明, 甘卫东. 2022版欧洲泌尿外科学会肾细胞癌诊疗指南更新要点解读[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(02): 100-104.
[10] 魏勇, 沈露明, 成向明, 苏健, 朱清毅. 机器人辅助单孔腹腔镜经腹膜后入路治疗马蹄肾合并肾癌一例报告[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2022, 16(06): 571-573.
[11] 吕逸清, 谢华, 周立军, 陈艳, 汪亚平, 陈方. 儿童机器人辅助腹腔镜下Xp11.2易位/TFE3基因融合相关性肾癌根治术的初步探讨[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2022, 16(04): 325-330.
[12] 马文亮, 董翔, 卓然, 刘宁, 李笑弓, 张古田, 郭宏骞, 甘卫东. 单中心评估保留肾单位手术在cT1期Xp11.2易位型肾癌的可行性[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2021, 15(02): 97-102.
[13] 袁雨涵, 杨盛力. 体液和组织蛋白质组学分析在肝癌早期分子诊断中的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 883-888.
[14] 向志强, 郭萍, 杨长青, 魏子白. 长链非编码RNA与胃癌作用机制及诊断预后研究进展[J/OL]. 中华消化病与影像杂志(电子版), 2021, 11(06): 291-295.
[15] 肖贵宝, 尼玛卓玛, 王峰, 王晋龙. 高原地区单中心五年肾癌临床病理特点分析[J/OL]. 中华临床医师杂志(电子版), 2022, 16(07): 647-651.
阅读次数
全文


摘要