miR-602、miR-452表达与肝癌术后复发转移及预后的关系研究

The relationship between the expression of mi R-602 and miR-452 and the recurrence,metastasis and prognosis of hepatocellular carcinoma

目的探究微小RNA-602(mi R-602)、微小RNA-452(mi R-452)表达与肝癌术后复发转移及预后的关系。方法选取2014年12月~2018年12月在我院确诊并行手术切除的原发性肝癌患者72例,术中收集癌组织及癌旁正常组织,采用RT-PCR法检测其mi R-602、mi R-452相对表达量,比较未发生和发生复发转移患者mi R-602、mi R-452相对表达量,Spearman检验分析mi R-602、mi R-452与肝癌术后复发转移的相关性,ROC曲线分析mi R-602、mi R-452预测肝癌术后复发转移的价值,COX回归模型及Kaplan-Meier法分析mi R-602、mi R-452表达与肝癌术后预后的关系。结果mi R-602、mi R-452在肝癌组织中的相对表达量较癌旁正常组织显著增加[(3.76±1.20)vs(0.76±0.16),t=21.027,P<0.001(;3.15±0.98)vs(0.45±0.07),t=23.318,P<0.001];发生复发转移患者mi R-602、mi R-452相对表达量较未发生复发转移患者显著增加[(4.12±1.47)vs(1.02±0.78),t=-10.978,P<0.001(;3.77±1.15)vs(0.76±0.64),t=-13.422,P<0.001];miR-602、miR-452均与肝癌术后复发转移呈正相关(r=0.501、0.548,P<0.001);mi R-602、mi R-452联合预测肝癌术后复发转移的AUC为0.900,敏感性为92.35%,特异性为88.10%;临床分期及mi R-602、mi R-452表达上调是肝癌术后预后的危险因素(P<0.05);mi R-602相对表达量>3.51患者肝癌术后2年病死率显著高于mi R-602相对表达量≤3.51患者[31.23%vs 7.02%,Log-rank(χ^(2))=2.436,P=0.038];miR-452相对表达量>2.01患者肝癌术后2年病死率显著高于mi R-452相对表达量≤2.01患者[29.65%vs 10.15%,Log-rank(χ^(2))=3.321,P=0.017]。结论mi R-602、mi R-452在肝癌组织中呈高表达,与肝癌术后复发转移及预后关系密切,有望成为肝癌术后复发转移、不良预后评估的候选临床标志物。

Objective To explore the relationship between the expression of microRNA-602(miR-602)and microRNA-452(miR-452)and postoperative recurrence,metastasis and prognosis of hepatocellular carcinoma(HCC).Methods 72 patients with primary liver cancer who were diagnosed and underwent surgical resection in our hospital from Dec 2014 to Dec 2018 were selected.Tumor tissues and adjacent normal tissues were collected during operation.The relative expression level of miR-602 and miR-452 were detected by RT-PCR.The relative expression level of miR-602 and miR-452 in patients with and without recurrence and metastasis were compared.The relationship between miR-602,miR-452 and recurrence and metastasis of HCC was analyzed by Spearman test.ROC was used to analyze the value of miR-602 and miR-452 in predicting the recurrence and metastasis of HCC.Cox regression model and Kaplan-Meier method were used to analyze the relationship between the expression of miR-602 and miR-452 and the prognosis of HCC.Results The relative expression levels of miR-602 and miR-452 in HCC tissues were significantly higher than those in adjacent normal tissues[(3.76±1.20)vs(0.76±0.16),t=21.027,P<0.001,(3.15±0.98)vs(0.45±0.07),t=23.318,P<0.001].The relative expression levels of miR-602 and miR-452 in patients with recurrence and metastasis were significantly higher than those in patients without recurrence and metastasis[(4.12±1.47)vs(1.02±0.78),t=-10.978,P<0.001,(3.77±1.15)vs(0.76±0.64),t=-13.422,P<0.001].miR-602 and miR-452 were positively correlated with postoperative recurrence and metastasis of hepatocellular carcinoma(r=0.501,0.548,P<0.001).AUC of miR-602 combined with miR-452 in predicting postoperative recurrence and metastasis of hepatocellular carcinoma was 0.900,sensitivity was 92.35%,specificity was 88.10%.Clinical stage and up-regulated expression of miR-602 and miR-452 were risk factors for postoperative prognosis of hepatocellular carcinoma(P<0.05).The 2-year mortality of patients with miR-602>3.51 was significantly higher than that of patients with miR-602≤3.51[31.23%vs 7.02%,Log-rank(χ^(2))=2.436,P=0.038].The 2-year mortality of patients with miR-452>2.01 was significantly higher than that of patients with miR-452≤2.01[29.65%vs 10.15%,Log-rank(χ^(2))=3.321,P=0.017].Conclusion miR-602 and miR-452 are highly expressed in HCC tissues,which are closely related to postoperative recurrence,metastasis and prognosis of HCC,and are expected to become candidate clinical markers for postoperative recurrence,metastasis and poor prognosis evaluation of HCC.