黏蛋白3A基因甲基化与神经母细胞瘤患儿预后的关系

Relationship between methylation status of mucoprotein 3A gene and prognosis in children with neuroblastoma

目的探讨黏蛋白3A（MUC3A）基因甲基化状态与神经母细胞瘤（NB）患儿预后的关系。方法选取2013年1月至2015年12月莱芜市妇幼保健院病理科收集的92例经病理学证实的NB患儿瘤体组织切片。其中男43例，女49例；年龄3个月～13岁，其中≤1岁31例，〉1岁61例。采用甲基化特异性聚合酶链反应技术检测92例NB组织中MUC3A基因甲基化状态，并分析MUC3A基因甲基化状态与NB患儿临床病理特征的关系。依据MUC3A基因甲基化状态分组比较MUC3A基因甲基化阳性组与阴性组患儿的3年生存率及生存期。结果年龄〉1岁、病理类型为分化差＋未分化、临床分期为Ⅲ＋Ⅳ期、MYCN基因扩增患儿的MUC3A基因甲基化发生率（86．89％、91．80％、90．32％、81．82％）均显著高于年龄≤1岁、病理类型为分化良好、临床分期为Ⅰ＋Ⅱ期、MYCN基因未扩增的患儿（38．71％、29．03％、30．00％、42．31％），差异均有统计学意义（χ2=23．007、39．059、35．480、14．043，均P〈0．001）。MUC3A基因甲基化阳性患儿的3年生存率（26．15％）显著低于MUC3A基因甲基化阴性患儿（66．67％），差异有统计学意义（χ2=13．283，P〈0．001）。MUC3A基因甲基化阳性患儿的3年中位生存期为19个月，显著短于MUC3A基因甲基化阴性患儿（32个月），差异有统计学意义（log-rank ;χ2=5．910，P=0．015）。结论MUC3A基因甲基化阳性提示NB患儿预后不良。

Objective To investigate the relationship between the methylation status of mucoprotein 3A （ MUC3A ） gene and the prognosis of children with neuroblastoma（NB）. Methods A pathological section of 92 cases of NB from January 2013 to December 2015 in Department of Pathology ,Children and Women＇s Heahhcare Hospital of Laiwu City, were colected. There were 43 males and 49 females;and their ages ranged from 3 months to 13 years old, in which 31 cases were less than 1 year old,and 61 cases were over 1 year old. Methylation specific polymerase chain reaction was used to detect the methylation status of MUC3A gene in 92 cases of NB, and the relationship between the methylation status of MUC3A gene and the clinicopathological features of NB were analyzed. According to the methylation status of MUC3A gene ,the 3 -year survival rate and survival time of the MUC3A gene methylation positive group and the negative group were compared. Results For those over 1 year old,the pathological types were differentiated ＋ undifferentiated and in clinical stage of stage Ⅲ ＋Ⅳ,their MYCN gene amplification,MUC3A gene methylation incidence （86.89% ,91.80% ,90.32% ,81.82% ） were significantly higher than those less than 1 year old,whose pathological types were well differentiated and in clinical stage of Ⅰ ＋ Ⅱ, MYCN gene was not amplified （38.71%, 29.03% ,30.00% , 42.31% ） , and the differences were statistically significant （χ2 = 23. 007,39. 059,35. 480, 14. 043, all P 〈 0.001 ）. The 3 year survival rate of MUC3A gene methylation positive children （ 26.15% ） was significantly lower than that of MUC3A gene methylation negative children （66.67%） , and the difference was statistically significant （χ2 = 13. 283 ,P 〈0.001 ）. The median survival time of MUC3A gene methylation positive children in 3 -year old children was 19 months, significantly shorter than that of MUC3A gene methylation negative children （ 32 months）, and the difference was statistically significant （log- rank ：χ2 = 5. 910 ,P = 0.015）. Conclusion The positive methylation of MUC3A gene suggests that children with NB have poor prognosis.