miR-103和AXIN2在弥漫大B细胞淋巴瘤中的表达及意义

Expression and significance of MiR-103 and AXIN2 in patients with diffuse large B-cell lymphoma

目的分析微小RNA-103(miR-103)和轴抑制因子2(AXIN2)在弥漫大B细胞淋巴瘤(DLBCL)组织中表达情况,并探讨二者关系及临床意义。方法选取2011年1月至2013年12月接受手术治疗的弥漫大B细胞淋巴瘤(DLBCL)患者110例作为受试对象,另选取同期行手术治疗的85例淋巴结反应性增生患者作为对照组,术中留取组织标本。采用免疫组化EnVision两步法检测DLBCL组织中AXIN2蛋白表达,采用实时定量PCR(qRT-PCR)检测不同组织中miR-103、AXIN2 mRNA表达水平;分析二者表达与临床特征及5年总体生存率(OS)关系。结果DLBCL组织中AXIN2蛋白阳性表达率为23.64%,non-GCB型明显高于GCB型(P<0.05)。DLBCL组织miR-103表达水平显著高于对照组淋巴结组织(P<0.05),AXIN2 mRNA表达水平明显低于对照组淋巴结组织(P<0.05)。miR-103、AXIN2 mRNA表达与DLBCL患者年龄、性别及β2-MG水平无关(P>0.05),与DLBCL患者Ann Arbor分期、IPI评分、Hans分型均有关(P<0.05)。DLBCL组织中miR-103与AXIN2 mRNA表达呈负相关(P<0.05)。miR-103低表达者5年OS高于高表达者,AXIN2 mRNA高表达者5年OS高于低表达者,差异均有统计学意义(P<0.05)。COX回归多因素分析可知,Hans分型、miR-103及AXIN2 mRNA表达均是影响DLBCL患者预后的独立危险因子(P<0.05)。结论DLBCL患者miR-103高表达、AXIN2低表达,检测二者表达水平有助于提高DLBCL患者临床分型准确性,并可作为评估患者预后的重要标志物。

Objective To investigate the expression of micro RNA-103(miR-103)and axis inhibitor 2(AXIN2)in patients with diffuse large B-cell lymphoma(DLBCL),and to explore their correlation and clinical significance.Methods A total of 110 patients with DLBCL who underwent surgical treatment in our hospital from January 2011 to December 2013 were enrolled in the study,at the same time,the other 85 patients with reactive lymph node hyperplasia who underwent surgical treatment in our hospital were enrolled as control group.The tissue specimens were collected during the operation.The expression levels of AXIN2 protein in DLBCL tissues were detected by immunohistochemical EnVision two-step method,moreover,the real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expressions of miR-103 and AXIN2 in different tissues.In addition the correlation between their expressions and clinical characteristics as well as 5-year overall survival rate(OS)was analyzed.Results The positive expression rate of AXIN2 protein in DLBCL was 23.64%,which in non-GCB type was significantly higher than that of GCB type(P<0.05).The expression levels of miR-103 in DLBCL tissues were significantly higher than those in control group(P<0.05),however,the expression levels of AXIN2 were significantly lower than those in control group(P<0.05).The expression levels of miR-103 and AXIN2 mRNA were not correlated with patient’s age and sex as well asβ2-MG levels in patients with DLBCL(P>0.05),however,which were related to Ann Arbor stage,IPI score and Hans classification in patients with DLBCL(P<0.05).There was a negative correlation between the expressions of miR-103 and AXIN2 mRNA in patients with DLBCL(P<0.05).The 5-year OS rate in miR-103 low-expression group was significantly higher than that in high-expression group,and the 5-year OS rate in AXIN2 high-expression group was significantly higher than that in in AXIN2 low expression group(P<0.05).Multivariate COX regression analysis showed that Hans typing,miR-103 and AXIN2 mRNA expressions were independent risk factors for the prognosis of patients with DLBCL(P<0.05).Conclusion The expression levels of miR-103 are higher and those of AXIN2 are lower in patients with DLBCL,and to detect their expression levels is helpful to improve the accuracy of clinical classification of DLBCL,which can regarded as an important marker for evaluating the prognosis of patients with DLBCL.