摘要
目的 探讨外泌体微小RNA(miR)-133a在透明细胞肾细胞癌(ccRCC)中的表达及临床意义。方法 收集2015年9月至2019年1月在我院行根治性肾切除术的293例ccRCC患者的血清样本,另外收集200例健康体检者的血清样本作为对照组。提取血清及组织外泌体总RNA,采用TaqMan低密度芯片(TLDA)鉴定差异表达的miRNA,并通过实时荧光定量PCR(qPCR)进行验证。随访患者的总生存期(OS)和无病生存期(DFS)。结果 与健康对照组血清和癌旁正常组织比较,TLDA筛选得到3个在ccRCC患者血清外泌体和肿瘤组织中差异表达的miRNAs(miR-133a、miR-210、miR-7-1)。qPCR证实外泌体miR-133a表达在ccRCC患者中显著下调(P<0.001)。ccRCC患者外泌体miR-133a表达与肿瘤组织表达呈正相关(r=0.467,P<0.001)。受试者工作特征(ROC)曲线证实血清外泌体miR-133a诊断ccRCC曲线下面积(AUC)为0.78(95%CI:0.747~0.729)。术前血清外泌体miR-133a表达与TNM分期、Fuhrman分级有关(P<0.05),与肾功能指标无关(P>0.05)。术前血清外泌体miR-133a高表达患者的DFS和OS均长于低表达者(P<0.001)。Cox风险比例回归分析显示血清外泌体miR-133a是影响ccRCC患者OS的独立预后因素[HR=0.486(95CI:0.226~1.043);P=0.034]。结论 血清外泌体miR-133a与ccRCC的发生、发展及预后密切相关,可能是预测ccRCC患者预后的生物标志物。
Objective To investigate the expression and clinical significance of exosomal microRNAs(miR-133a) in clear cell renal cell carcinoma(ccRCC). Methods Serum samples were collected from 293 patients with ccRCC who underwent radical nephrectomy in our hospital from September 2015 to January 2019, and another 200 healthy people were collected as control group. Total RNA was extracted from serum and tissue exosomes, and differentially expressed mirnas were identified by TaqMan low-density microarray(TLDA), and verified by real-time fluorescence quantitative PCR(qPCR). Overall survival(OS) and disease-free survival(DFS) were followed up. Results Compared with healthy control group serum and adjacent normal tissue, three miRNAs(miR-133a, miR-210, miR-7-1) were differentially expressed in serum exosomes and tumor tissues of ccRCC patients by TLDA screening. The expression of exosomes miR-133a was significantly down-regulated in ccRCC patients by qPCR(P<0.001). The expression of exosome miR-133a in ccRCC patients was positively correlated with that in tumor tissues(r=0.467, P<0.001). Receiver operating characteristic(ROC) curves confirmed that the area under the ccRCC curve(AUC) for the diagnosis of serum exosome miR-133a was 0.78(95%CI: 0.747-0.729). The expression of preoperative serum exosome miR-133a was correlated with TNM stage and Fuhrman grade(P<0.05), but not renal function index(P>0.05). The DFS and OS of patients with high expression of serum exosome miR-133a before surgery were both longer than those with low expression(P<0.001). Cox proportional regression analysis showed that serum exosome miR-133a was an independent prognostic factor for OS in patients with ccRCC [HR=0.486(95CI: 0.226-1.043);P=0.034]. Conclusion Serum exosome miR-133a is closely related to the occurrence, development and prognosis of ccRCC, and may be a biomarker to predict the prognosis of patients with ccRCC.
作者
孙怀鑫
邵翔
徐德宇
陈彬
刘倩盼
刘曼
李玉婷
SUN Huaixin;SHAO Xiang;XU Deyu;CHEN Bin;LIU Qianpan;LIU Man;LI Yuting(Department of Nephrology,Suzhou Jiulong Hospital,School of Medicine,Shanghai Jiaotong University,Suzhou 215028,China)
出处
《临床肿瘤学杂志》
CAS
2023年第2期105-111,共7页
Chinese Clinical Oncology
基金
苏州市科技计划资助项目(SKJY2021030)。
作者简介
通讯作者:邵翔,E-mail:385534405@qq.com。
