子宫内膜癌组织中miR-128-3p、Notch1 mRNA、BMI1 mRNA的表达变化及其意义

Expression and clinical significance of miR-128-3p,Notch1 mRNA and BMI1 mRNA in endometrial cancer tissues

目的观察子宫内膜癌组织中微小RNA-128-3p(miRNA-128-3p)及缺口受体1(Notch1)、B细胞特异性莫洛尼鼠白血病病毒整合位点1(BMI1)mRNA的表达变化,并探讨其临床意义。方法选取子宫内膜癌及其癌旁组织各150例份,采用qRT-PCR法检测两组织miR-128-3p及Notch1、BMI1 mRNA,Pearson相关分析法分析三指标间及其与子宫内膜癌临床病理特征的关系,K-M法绘制不同miR-128-3p、Notch1 mRNA、BMI1 mRNA表达子宫内膜癌患者生存曲线,多因素Cox回归分析法分析子宫内膜癌患者死亡影响因素。结果子宫内膜癌组织中miR-128-3p、Notch1 mRNA、BMI1 mRNA相对表达量分别为0.66±0.22、2.79±0.43、1.25±0.26,癌旁组织分别为1.00±0.21、2.02±0.37、0.76±0.28,两者比较,P均<0.05。子宫内膜癌组织中miR-128-3p与Notch1 mRNA、BMI1 mRNA表达呈负相关(r分别为-0.744、-0.733,P均<0.05),Notch1 mRNA与BMI1 mRNA表达呈正相关(r=0.803,P<0.05)。miR-128-3p、Notch1 mRNA、BMI1 mRNA表达均与子宫内膜癌分化程度、国际妇产科联盟(FIGO)分期、血管侵犯、淋巴结转移有关(P均<0.05)。miR-128-3p≥0.66、0.66者术后3年累积生存率分别为80.56%(58/72)、57.69%(45/78),两者比较,P<0.05;Notch1 mRNA≥2.79、<2.79者术后3年累积生存率分别为60.00%(45/75)、77.33%(58/75),两者比较,P<0.05;BMI1 mRNA≥1.25、<1.25者术后3年累积生存率分别为55.84%(43/77)、82.19%(60/73),两者比较,P<0.05。FIGO分期Ⅲ~Ⅳ期、淋巴结转移、Notch1 mRNA≥2.79、BMI1 mRNA≥1.25为子宫内膜癌患者死亡独立风险因素,miR-128-3p≥0.66为独立保护因素。结论子宫内膜癌组织中miR-128-3p低表达,Notch1、BMI1 mRNA高表达,均与子宫内膜癌分化程度、FIGO分期、血管侵犯、淋巴结转移有关,是子宫内膜癌患者死亡的影响因素,可能成为患者预后评估的生物标志物。

Objective To observe the changes in the expression levels of microRNA-128-3 p(miRNA-128-3 p)and Notch1 and B-cell-specific Moloney murine leukemia virus integration site 1(BMI1)mRNA in the endometrial cancer tissues and to explore their clinical significance.Methods Totally 150 cases of endometrial cancer tissues and their paracancerous tissues were selected,and miR-128-3 p and Notchl and BMI1 mRNA were detected by qRT-PCR Pearson correlation analysis was used to analyze the relationship between the three indicators and their relationship with the clinicopathological characteristics of endometrial cancer.Survival curves of endometrial cancer patients with different miR-128-3 p,Notch1 mRNA and BMI1 mRNA expression were plotted by the K-M method,and the factors influencing the death of endometrial cancer patients were analyzed by multi-factor Cox regression analysis.Results The expression levels of miR-128-3 p,Notch1 mRNA and BMI1 mRNA in the endometrial cancer tissues were 0.66±0.22,2.79±0.43,and 1.25±0.26,respectively,and they were 1.00±0.21,2.02±0.37,and 0.76±0.28 in the paracancerous tissues,respectively,with statistically significant difference(all P<0.05).The miR-128-3 p was negatively correlated with Notchl mRNA and BMI1 mRNA expression in the endometrial cancer tissues(r=-0.744,-0.733,both P<0.05),and Notchl mRNA was positively correlated with BMI1 mRNA expression(r=0.803,P<0.05).MiR-128-3 p,Notch l mRNA,and BMI1 mRNA expression were all associated with the degree of endometrial cancer differentiation,International Federation of Gynecology and Obstetrics(FIGO)stage,vascular invasion,and lymph node metastasis(all P<0.05).C.umulative survival rates at 3 years after surgery in patients with miR-128-3 p≥0.66 and 0.66 were 80.56%(58/72)and 57.69%(45/78),respectively,with statistically significant difference(all P<0.05).Cumulative survival rates at 3 years after surgery were60.00%(45/75)and 77.33%(58/75)in those with Notch1 mRNA>2.79 and<2.79,respectively,and there was statistically significant difference(all P<0.05).The cumulative survival rates at 3 years after surgery were 55.84%(43/77)and 82.19%(60/73)in those with BMI1 mRNA≥l.25 and<1.25,respectively,and there was statistically significant difference(all P<0.05).FIGO stageⅢ-Ⅳ,lymph node metastasis,Notch1 mRNA≥2.79,and BMI1 mRNA≥1.25 were independent risk factors for death of endometrial cancer patients,and miR-128-3 p≥0.66 was independent protective factor.Conclusion Low expression of miR-128-3 p and high expression of Notchl and BMI1 mRNA in endometrial cancer tissues are all associated with the degree of differentiation,FIGO stage,vascular invasion and lymph node metastasis of endometrial cancer,which are influential factors for the death of endometrial cancer patients and may become biomarkers for prognostic assessment of patients.