微小RNA-101在结肠癌组织的表达及其与患者预后的关系

Expression of microRNA-101 in colon cancer tissues and its correlation with prognosis of patients

目的 探讨微小RNA（miRNA,miR）-101在结肠癌组织中表达及与患者预后的关系.方法 选取择期行根治性手术治疗的结肠癌患者137例,利用实时荧光定量聚合酶链反应（FQ-PCR）检测结肠癌及癌旁组织中miR-101和Zeste基因增强子人类同源物-2（EZH-2）基因表达,根据结肠癌组织中miR-101表达量的四分位数间距,将患者分为高表达组[表达量≥上四分位数（P25）]和低表达祖（表达量＜ P25）,所有患者随访至2015年7月31日,利用Kaplan-Meier法分析患者术后总体生存时间,利用Cox比例风险模型分析影响患者术后总体生存时间的相关因素.结果 结肠癌组织中miR-101表达量显著低于癌旁组织,而EZH-2 mRNA表达量则高于癌旁组织,差异均有统计学意义（P＜0.05）;结肠癌组织中miR-101和EZH-2 mRNA表达量均与分化程度、TNM分期、淋巴结转移和远处转移有关（P＜0.05）;Pearson相关分析显示,结肠癌组织中miR-101表达量与EZH-2 mRNA表达量呈负相关（r=-0.348,P＜0.05）;生存分析显示,高表达组患者术后总体生存时间为51.5个月,显著高于低表达组的30.9个月,差异有统计学意义（x2=10.903,P＜0.01）;Cox比例风险模型分析显示,miR-101[风险比（HR）=0.492,95％可信区间（CI）：0.334 ～0.795,P＜0.05]和TNM分期（HR=2.576,95％CI：1.572～3.874,P＜0.05）是影响结肠癌患者术后总体生存时间的独立风险因素.结论 结肠癌组织中miR-101呈低表达,可能与结肠癌发生及转移过程有关,可作为患者术后生存时间的预测指标,其机制可能与上调EZH2表达有关.

Objective To investigate the expression of microRNA （miRNA,miR）-101 in colon cancer tissues and its correlation with prognosis of patients.Methods 137 cases of colon cancer undergoing elective radical surgery from June 2008 to July 2010 at the Affiliated Tumor Hospital of Zhengzhou University were selected.The expression levels of miR-101 and enhancer of zeste homolog-2 （EZH-2） gens in colon cancer tissues and adjacent non-cancerous tissues were detected by real-time fluorescent quantitative polymerase chain reaction（FQ-PCR）.According to the interquartile of the expression level of miR-101 in colon cancer tissue,the patients were divided into high expression group （expression level ≥ P25） and low expression group （expression level 〈 P25）.All patients were followed up until July 31,2015.The overall survival time of patients after surgery was analyzed by Kaplan-Meier method.The relevant affecting factors of the overall survival time were analyzed by using Cox proportional hazards model.Results The expression levels of miR-101 in colon cancer tissues were lower than in the adjacent tissues,while the expression levels of EZH-2 mRNA were higher than the adjacent tissues with the differences being statistically significant （P 〈 0.05）.The expression levels of miR-101 and EZH-2 mRNA were related with the degree of differentiation,TNM stage,lymph node metastasis and distant metastasis （P 〈0.05）.Pearson correlation analysis revealed that the expression level of miR-101 in colon cancer tissue was negatively correlated with the expression level of EZH-2 mRNA （r =-0.348,P 〈 0.05）.Survival analysis showed that the overall survival time of patients in high expression group was 51.5 months,which was significantly longer than 30.9 months in low expression group with the difference being statistically significant （x2=10.903,P〈 0.01）.Cox proportional hazards model analysis indicated that miR-101 [hazard ratio （HR） =0.492,95% confidence interval （CI）：0.334-0.795,P 〈 0.05） and TNM stage （HR =2.576,95% CI：1.572-3.874,P 〈 0.05） were independent risk factors for overall survival time of colon cancer patients after surgery.Conclusion The low expression of miR-101 in colon cancer tissue might be related with the occurrence and metastasis of colon cancer,which might be related with the up-regulated expression of EZH2.miR-101 could be used as predicting indicator of survival time of patients.