子宫内膜癌组织miR-139-5p、miR-379-5p表达水平与侵袭相关基因和预后的关系研究

Study on the Relationship between the Expression Levels of miR-139-5p and miR-379-5p of Endometrial Cancer Tissue and Invasion Related Genes and Prognosis

目的:研究子宫内膜癌组织微小核糖核酸(miR)-139-5p、miR-379-5p表达水平与侵袭相关基因和预后的关系。方法:选取2018年12月-2019年12月于西安交通大学第二附属医院行手术治疗的105例子宫内膜癌患者。收集术后癌组织与癌旁组织标本,实时荧光定量聚合酶链反应(PCR)法检测癌组织与癌旁组织miR-139-5p、miR-379-5p及侵袭基因[高迁徙率蛋白1(HMGB1)、分泌型蛋白Dikkopf-1(DKK1)]的表达水平。Pearson法分析癌组织miR-139-5p、miR-379-5p表达水平与侵袭基因表达水平的相关性。根据癌组织miR-139-5p、miR-379-5p不同表达水平将患者分为miR-139-5p高表达组(n=62)与低表达组(n=43)、miR-379-5p高表达组(n=69)与低表达组(n=36),分析miR-139-5p、miR-379-5p高低表达与患者临床病理特征关系。随访3年,统计患者死亡情况。采用Kaplan-Meier法分析miR-139-5p、miR-379-5p表达水平与子宫内膜癌患者预后的关系。结果:癌组织中的miR-139-5p、miR-379-5p表达水平低于癌旁组织(P<0.05)。癌组织中DKK1表达量低于癌旁组织,HMGB1表达量高于癌旁组织(P<0.05)。miR-139-5p、miR-379-5p表达水平与DKK1表达量呈正相关,与HMBG1表达量呈负相关(P<0.05)。miR-139-5p、miR-379-5p高、低表达组在国际妇产科联盟(FIGO)分期、淋巴结转移、脉管浸润、肌层浸润方面比较,差异有统计学意义(P<0.05)。105例患者随访3年,期间失访3例、死亡21例,3年生存率为79.41%(81/102)。miR-139-5p低表达组3年总生存率为61.90%(26/42),低于miR-139-5p高表达组的91.67%(55/60);miR-379-5p低表达组3年总生存率为62.86%(22/35),低于miR-379-5p高表达组的88.06%(59/67)。结论:子宫内膜癌组织中miR-139-5p、miR-379-5p表达水平下调,可能与侵袭基因表达量异常以及患者的预后不良有关。

Objective:To study the relationship between the expression levels of microribonucleic acid(miR)-139-5p and miR-379-5p of endometrial cancer tissue and invasion related genes and prognosis.Methods:105 patients with endometrial cancer who underwent surgical treatment in The Second Affiliated Hospital of Xi'an Jiaotong University from December 2018 to December 2019 were selected.The postoperative cancer tissue and cancer adjacent tissue samples from patients were collected,and the expression levels of miR-139-5p,miR-379-5p,and invasion genes[high mobility group box 1(HMGB1),secretory protein Dikkopf-1(DKK1)]of cancer tissue and cancer adjacent tissue were detected by real time fluorescence quantitative polymerase chain reaction(PCR).Pearson method was used to analyze the correlation between the expression levels of miR-139-5p,miR-379-5p and invasion gene expression in cancer tissue.According to the different expression levels of miR-139-5p and miR-379-5p in cancer tissues,patients were divided into miR-139-5p high expression group(n=62)and low expression group(n=43),miR-379-5p high expression group(n=69)and low expression group(n=36),and the relationship between the high expression and low expression of miR-139-5p,and miR-379-5p and the clinical pathological characteristics of patients were analyzed.Followed up for 3 years,and patients death situation were counted.The relationship between the expression levels of miR-139-5p,miR-379-5p and the prognosis of patients with endometrial cancer were analyzed by the Kaplan-Meier method.Results:The expression levels of miR-139-5p and miR-379-5p of cancer tissue were lower than those of cancer adjacent tissue(P<0.05).The expression level of DKK1 of cancer tissues was lower than that of cancer adjacent tissue,while the expression level of HMGB1 was higher than that of cancer adjacent tissue(P<0.05).The expression levels of miR-139-5p and miR-379-5p were positively correlated with DKK1 expression,and negatively correlated with HMBG1 expression(P<0.05).The high and low expression groups of miR-139-5p and miR-379-5p showed statistically significant differences in International Federation of Gynecology and Obstetrics(FIGO)staging,lymph node metastasis,vascular invasion,and degree of muscle infiltration(P<0.05).105 patients were followed up for 3 years,there were 3 cases of lost visits and 21 deaths during the period,and the 3-year survival rate was 79.41%(81/102).The 3-year overall survival rate of the miR-139-5p low expression group was 61.90%(26/42),which lower than 91.67%(55/60)of the miR-139-5p high expression group.The 3-year overall survival rate of the miR-379-5p low expression group was 62.86%(22/35),which lower than88.06%(59/67)of the miR-379-5p high expression group.Conclusion:The expression levels of miR-139-5p and miR-379-5p of endometrial cancer tissues are downregulated,which may be related to abnormal expression of invasion genes and poor prognosis of patients.