肝癌组织中miR-1470 PATZ1表达水平与患者5年内预后的关系

Association between microRNA-1470 and PATZ1 Expression in Hepatocellular Carcinoma Tissues and Patient Prognosis within 5 Years

目的:探讨肝癌组织中微小RNA-1470(miR-1470)、POZ结构域和AT结合基序锌指蛋白1(PATZ1)表达水平与患者5年内预后的关系。方法:选取2015年9月至2018年8月在邯郸市中心医院接受根治术治疗的肝癌患者135例,术中留取肝癌组织及相应癌旁正常组织(距肿瘤边缘2cm以上的正常肝脏组织)。采用免疫组织化学法检测PATZ1蛋白表达;采用实时荧光定量PCR法检测miR-1470、PATZ1 mRNA表达;术后进行5年的随访,统计5年总生存率。比较肝癌组织和癌旁正常组织中miR-1470、PATZ1 mRNA和蛋白表达情况;分析肝癌组织中miR-1470、PATZ1 mRNA表达与临床病理参数的关系,二者表达的相关性及与预后的关系,影响预后的危险因素;双荧光素酶报告基因实验验证miR-1470与PATZ1的靶向关系。结果:肝癌组织PATZ1蛋白阳性表达率明显低于癌旁正常组织(P<0.05)。与癌旁正常组织比较,肝癌组织中miR-1470表达水平明显升高,PATZ1 mRNA表达水平明显降低(P<0.05)。肝癌组织中miR-1470、PATZ1 mRNA低表达、高表达患者在血清甲胎蛋白(AFP)水平、中国肝癌分期方案(CNLC)分期及有无脉管癌栓方面,差异均有统计学意义(P<0.05)。肝癌组织中miR-1470与PATZ1 mRNA表达呈负相关(P<0.05)。miR-1470低表达患者、PATZ1 mRNA高表达患者5年总生存率分别明显高于miR-1470高表达患者、PATZ1 mRNA低表达患者(P<0.05)。CNLC分期Ⅲ期、脉管癌栓、miR-1470高表达及PATZ1 mRNA低表达是影响肝癌患者预后不良的独立危险因素(P<0.05)。miR-1470可负向调控PATZ1表达。结论:肝癌组织中miR-1470表达上调,PATZ1表达下调,两者呈负相关,均可作为评估肝癌患者预后的生物标记物,且miR-1470可负向调控PATZ1表达。

Objective:To investigate the association between the expression levels of microRNA-1470(miR-1470),POZ domain and AT-binding motif zinc finger protein 1(PATZ1)in hepatocellular carcinoma(HCC)tissues and patient prognosis within 5 years.Methods:A total of 135 patients with HCC who underwent radical resection at Handan Central Hospital from September 2015 to August 2018 were enrolled in this study.HCC tissues and corresponding adjacent normal tissues(normal liver tissues more than 2 cm away from the tumor margin)were collected during surgery.Immunohistochemistry was used to detect PATZ1 protein expression;real-time fluorescence quantitative PCR was used to detect miR-1470 and PATZ1 mRNA expression.Patients were followed up for 5 years,and 5-year overall survival rates were calculated.The expression of miR-1470 and PATZ1 mRNA and protein in HCC tissues and adjacent normal tissues was compared;the relationship between miR-1470 and PATZ1 mRNA expression and clinicopathological parameters,their correlation,and their association with prognosis were analyzed;and the risk factors affecting prognosis were identified.Dual luciferase reporter gene assay was used to verify the target relationship between miR-1470 and PATZ1.Results:The positive expression rate of PATZ1 protein in HCC tissues was significantly lower than that in adjacent normal tissues(P<0.05).Compared with adjacent normal tissues,the expression level of miR-1470 was significantly upregulated and the expression level of PATZ1 mRNA was significantly downregulated in HCC tissues(P<0.05).Patients with low miR-1470 and high PATZ1 mRNA expression in HCC tissues had significant differences in serum alpha-fetoprotein(AFP)level,China Liver Cancer Staging System(CNLC)stage,and the presence or absence of vascular tumor thrombus(P<0.05).The expression of miR-1470 and PATZ1 mRNA was negatively correlated in HCC tissues(P<0.05).The 5-year overall survival rates of patients with low miR-1470 expression and high PATZ1 mRNA expression were significantly higher than those of patients with high miR-1470 expression and low PATZ1 mRNA expression(P<0.05).CNLC stage III,vascular tumor thrombus,high miR-1470 expression,and low PATZ1 mRNA expression were independent risk factors for poor prognosis in HCC patients(P<0.05).miR-1470 could negatively regulate PATZ1 expression.Conclusion:miR-1470 is upregulated and PATZ1 is downregulated in HCC tissues,and the two are negatively correlated.Both can be used as biomarkers to evaluate the prognosis of HCC patients,and miR-1470 can negatively regulate PATZ1 expression.