关键词: 透明细胞肾细胞癌, 外泌体, 微小RNA-133a, 诊断, 预后

Abstract:

【Abstract】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.

Key words: Clear cell renal cell carcinoma')">

Clear cell renal cell carcinoma, Exosome, miRNA-133a, Diagnosis, Prognosis