微小RNA-375在甲状腺乳头状癌组织的表达及其临床意义

Expression of miR-375 in thyroid papillary carcinoma and its clinical significance

目的观察甲状腺乳头状癌(PTC)组织中微小RNA(miRNA,miR)-375表达,探讨其机制及其临床意义。方法选取2018年1月至2018年12月郑州大学第一附属医院甲状腺乳头状癌根治手术的患者60例,应用实时定量聚合酶链反应检测PTC组织和癌旁正常组织miR-375表达水平,应用甲基化特异性PCR法检测组织内miR-375上游CpG岛甲基化。应用受试者工作特征(ROC)曲线法分析miR-375对PTC的诊断效能;应用独立样本t检验分析PTC组织中miR-375表达水平和临床病理特征的相关性;应用检验分析miR-375上游甲基化率和其表达异常的相关性。结果PTC组织miR-375表达水平低于癌旁正常组织(0.824±0.182比1.079±0.212),差异有统计学意义(t=-7.080,P<0.05);当以组织miR-375表达水平≤0.8842作为诊断PTC的标准,此时敏感度和特异度分别86.7%、71.7%,约登指数为58.3%;PTC肿瘤TNM分期Ⅲ~Ⅳ期、淋巴结出现癌转移和出现神经或肌肉侵犯者,较肿瘤TNM分期Ⅰ~Ⅱ期、淋巴结未出现癌转移和无神经或肌肉侵犯者组织miR-375表达水平下降,差异有统计学意义(TNM分期,t=-5.365,P<0.01;淋巴结癌转移,t=-2.136,P<0.05;神经肌肉侵犯,t=-2.457,P<0.05);以截断值0.8842为分界点定义miR-375的表达水平,则所有120例组织中miR-375低表达者51例(42.5%),高表达者69例(57.5%);所有120例组织中miR-375上游CpG岛甲基化者60例(50.0%),非甲基化者60例(50.0%);miR-375低表达者上游CpG岛甲基化率(62.7%)较miR-375高表达者甲基化率(40.6%)高,差异有统计学意义(χ^2=5.763,P<0.05)。结论miR-375上游CpG岛甲基化可能导致miR-375表达下降,进而促进PTC的发生;PTC组织miR-375低表达提示PTC预后不良。

Objective To investigate the expression,potential mechanism and clinical significance of microRNA(miRNA,miR)-375 in thyroid papillary carcinoma(PTC).Methods A total of 60 patients diagnosed as PTC receiving radical thyroidectomy were analyzed.Real-time quantitative polymerase chain reaction was used to detect miR-375 expression levels in PTC tissues and adjacent normal tissues.Independent sample t test was used to analyze the correlation between miR-375 expression level and clinicopathological characteristics of PTC.Chi-square test was used to analyze the correlation between the upstream methylation rate of miR-375 and its abnormal expression.Results The expression levels of miR-375 in PTC tissues and para-cancer normal tissues were 0.824±0.182 and 1.079±0.212 respectively.The expression level of miR-375 in PTC tissues was significantly lower than that in the adjacent normal tissues(t=-7.080,P<0.05).When tissue miR-375 expression level of 0.8842 was used as the diagnostic criteria for PTC,the sensitivity and specificity were 86.7%and 71.7%respectively,the Youden index was 58.3%.The miR-375 expression level in PTC tissues with TNM stageⅢ-Ⅳ,pathological lymphatic metastasis,and tumor’s invasion of muscle or nerve was significantly decreased as compared with PTC tissues without these features(for TNM stage,t=-5.365,P<0.01;for lymphatic metastasis,t=-2.136,P<0.05;for invasion of muscle or nerve,t=-2.457,P<0.05).When the value of 0.8842 was taken as the cut-off point to define the expression level of miR-375,there were 51 cases(42.5%)with low miR-375 expression and 69 cases(57.5%)with high expression among 120 tissues.CpG island methylation upstream of miR-375 was observed in half of the cases(50%),while no methylation was observed in the other half(50%).The upstream CpG island methylation rate(62.7%)was significantly higher in the group with low miR-375 expression than in the group with high miR-375 expression(40.6%)(χ^2=5.763,P<0.05).Conclusion Upstream CpG island methylation of miR-375 may lead to decreased expression of miR-375,thereby promoting the occurrence of PTC.Low expression of miR-375 in PTC tissues suggests poor prognosis of PTC.