miR-222-3p在乙型肝炎病毒相关肝细胞癌血清外泌体中的表达及临床意义

Expression and clinical significance of miR-222-3p in serum exosomes of hepatitis B virus-associated hepatocellular carcinoma

目的探讨miR-222-3p在乙型肝炎病毒(HBV)相关肝细胞癌(HCC)血清外泌体中的表达及其与临床特征和预后的相关性。方法收集我院收治的604例HCC患者的临床病理资料,包括391例HBV-HCC患者(HBV-HCC组)和213例非HBV-HCC患者(非HBV-HCC组)。另选取288例慢性乙肝患者作为HBV组。采用实时荧光定量PCR法检测血清外泌体miR-222-3p表达水平,分析miR-222-3p表达与HBV-HCC患者不同临床特征的关系。采用受试者工作特征(ROC)曲线评估血清外泌体miR-222-3p对HBV-HCC的诊断价值;采用Kaplan-Meier生存曲线和Log-rank检验分析miR-222-3p表达水平与患者预后的相关性;采用Cox比例回归风险模型分析影响HBV-HCC患者预后的危险因素。结果HBV-HCC组患者血清外泌体miR-222-3p水平显著高于非HBV-HCC组和HBV组(P<0.001)。经ROC曲线分析,血清外泌体miR-222-3p用于HBV-HCC诊断(HBV-HCC组vs.HBV组、HBV-HCC组vs.非HBV-HCC组)的曲线下面积(AUC)分别为0.900(95%CI:0.878~0.922)、0.731(95%CI:0.692~0.771)。血清外泌体miR-222-3p的表达与患者HBV-DNA拷贝、天冬氨酸转氨酶(AST)、异常凝血酶原(DCP)、巴塞罗那临床肝癌(BCLC)分期有关(P<0.05)。HBV-HCC患者血清外泌体miR-222-3p高表达组和低表达组中位生存时间分别为2.66年、4.14年,总生存率分别为32.8%、35.7%(Log-rankχ^(2)=15.078,P<0.001)。经Cox比例风险回归模型分析,血清外泌体miR-222-3p表达水平升高是影响HBV-HCC患者预后的独立危险因素之一(P<0.05)。结论血清外泌体miR-222-3p与HBV-HCC的发生发展密切相关,其表达水平升高是影响HBV-HCC患者预后的独立危险因素。

Objective To investigate the expression of miR-222-3p in serum exosomes of hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC)and its correlation with clinical features and prognosis.Methods The clinicopathological data of 604 patients with HCC in our hospital were collected,including 391 patients with HBV-HCC(the HBV-HCC group)and 213 patients with non-HBV-HCC(the non-HBV-HCC group).And another 288 patients with chronic hepatitis B were selected as the HBV group.The expression level of serum exosome miR-222-3p was detected by real-time fluorescent quantitative PCR method,and the relationship between the expression of miR-222-3p and different clinical features of HBV-HCC patients was analyzed.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of serum exosome miR-222-3P for HBV-HCC;Kaplan-Meier survival curve and Log-rank test were used to analyze the correlation between the expression level of miR-222-3P and the prognosis of patients;Cox proportional hazards regression model was used to analyze the risk factors affecting the prognosis of patients with HBV-HCC.Results The level of serum exosome miR-222-3p in the HBV-HCC group was significantly higher than that in the non-HBV-HCC group and the HBV group(P<0.001).According to the ROC curve analysis,the area under the curve(AUC)of serum exosome miR-222-3p for the diagnosis of HBV-HCC(the HBV-HCC group vs.the HBV group,the HBV-HCC group vs.the non-HBV-HCC group)were 0.900(95%CI:0.878 to 0.922)and 0.731(95%CI:0.692 to 0.771),respectively.The expression of serum exosome miR-222-3p was related to the patient’s HBV-DNA copy,aspartate aminotransferase(AST),des-gamma-carboxy prothrombin(DCP)and Barcelona clinic liver cancer(BCLC)stage(P<0.05).The median survival time in the high expression group and the low expression group of serum exosome miR-222-3p in patients with HBV-HCC were 2.66 years and 4.14 years,respectivel y,and the overall survival rates were 32.8%and 35.7%,respectively(Log-rankχ^(2)=15.078,P<0.001).Cox proportional hazards regression model analysis showed that the elevated expression level of serum exosome miR-222-3p was one of the independent risk factors affecting the prognosis of patients with HBV-HCC(P<0.05).Conclusion Serum exosome miR-222-3p is closely related to the occurrence and development of HCC-HCC,and its elevated expression level is an independent risk factor affecting the prognosis of patients with HBV-HCC.