视网膜母细胞瘤组织中miR-132和叉头框蛋白A1的表达水平及意义

Expression levels and significance of miR-132 and FOXA1 in retinoblastoma

目的探讨视网膜母细胞瘤(Rb)组织中miR-132和叉头框蛋白A1(FOXA1)的表达水平及意义。方法选取2013年5月至2016年12月间西安市第四医院收治的手术治疗的60例Rb患者,采用qRT-PCR法检测Rb组织与癌旁组织中miR-132表达水平,用免疫组化法检测FOXA1水平,分析miR-132和FOXA1表达与Rb患者临床病理特征及预后的相关性。结果 miR-132在Rb组织中表达水平低于癌旁组织,差异有统计学意义(P <0.05)。免疫组织化学染色显示,Rb组织中FOXA1蛋白阳性表达率高于癌旁组织,差异有统计学意义(P <0.05)。以Rb组织中miR-132表达平均数,将Rb患者分为高表达组(≥0.64) 25例和低表达组(<0.64) 35例;以FOXA1蛋白免疫组织化学染色结果,将Rb患者分为FOXA1阳性组39例和FOXA1阴性组21例。分析发现,miR-132和FOXA1表达与肿瘤分化和视神经浸润有关(P <0.05),与性别、年龄、侧别和RB分期无关(P>0.05)。Kaplan-Meier生存分析可知,miR-132高表达组Rb患者3年累积生存率高于低表达组(70.4%vs 38.9%,P <0.05)。FOXA1阳性组Rb患者3年总生存率低于阴性组(30.8%vs 78.9%,P <0.05)。Cox回归模型单因素分析结果显示,病理分化、视神经浸润、miR-132低表达和FOXA1阳性表达是影响Rb患者不良预后的危险因素(P <0.05)。多因素分析结果显示,病理分化、视神经浸润、miR-132低表达和FOXA1阳性表达是影响Rb患者不良预后的独立危险因素(P <0.05)。结论Rb组织中miR-132低表达、FOXA1高表达,与患者病理分化、视神经浸和生存质量有关,可作为Rb患者潜在的预后标志物。

Objective To discuss the expressions and significance of miR-132 and forkhead-box protein A1( FOXA1) in retinoblastoma( Rb) tissues. Methods From May 2013 to December 2016,60 Rb patients undergoing operation at Xi’an Fourth Hospital were selected. Quantitative reverse transcriptasepolymerase chain reaction( qRT-PCR) method was used to detect the expression level of miR-132 in Rb tissues and paracancerous tissues. The levels of FOXA1 were detected by immunohistochemistry. The association between the expression of miR-132 and FOXA1 and the clinicopathological characteristics of Rb were analyzed. Results The expression level of miR-132 was significantly lower in Rb tissues than in paracancerous tissues( P < 0. 05). Immunohistochemistry showed that the positive expression rate of FOXA1 was higher in Rb tissues than in paracancerous tissues( P < 0. 05). Using the average expression level of miR-132 in Rb tissues,Rb patients were divided into patients with high expression of miR-132( ≥0. 64,25 patients) and patients with low expression of miR-132( < 0. 64,35 patients). Similarly,Rb patients were divided into patients with positive expression of FOXA1( 39 patients) and patients with negative expression of FOXA1( 21 patients). After analysis,it was found that the expression of miR-132 and FOXA1 was associated with pathological differentiation and optic nerve infiltration( all P < 0. 05) but not age,gender,lateralization and Rb stage. Kaplan-Meier survival analysis showed that the 3-year cumulative survival rate was significantly higher in patients with high expression of miR-132 than in patients with low expression of miR-132( 70. 4% vs. 38. 9%,P < 0. 05). The 3-year survival rate was significantly lower in patients in positive expression of FOXA1 than in patients with negative expression of FOXA1( 30. 8% vs. 78. 9%,P < 0. 05).Cox regression analysis showed that pathological differentiation,optic nerve infiltration,low expression of miR-132 and positive expression of FOXA1 were independent risk factors for adverse prognosis in Rb patients. Multivariate analysis showed that pathological differentiation,optic nerve infiltration,low expression of miR-132 and positive expression of FOXA1 were independent risk factors influencing prognosis in Rb patients. Conclusion The low expression of miR-132 and the positive expression of FOXA1 are associated with pathological differentiation,optic nerve infiltration and quality of life,which may be potential markers for prognosis of Rb.