神经母细胞瘤干细胞转录因子的表达与意义

Expressions of stem cell transcription factors in neuroblastoma and their significance

摘要:

目的 探索干细胞转录因子C-Myc、Sox2、Oct4、Klf4 在儿童神经母细胞瘤（NB）的表达及其意义。 方法 选取河北医科大学第四医院儿科53 例NB 病理标本作为实验组。实验组又分为Ⅲ期组和Ⅳ期组；节细 胞- 神经母细胞瘤组和神经母细胞瘤组；术前有骨髓浸润化疗组和术前无骨髓浸润无化疗组。另选取10 例 严重肾盂积水患儿手术后残余的正常肾上腺组织作为对照组。采用免疫组织化学法检测各标本中C-Myc、 Sox2、Oct4、Klf4 的表达情况，分析化疗对其表达的影响及其与临床分期、病理类型、性别、年龄等病理参 数的关系，并做相关性分析。结果 C-Myc、Sox2、Oct4、Klf4 阳性率表达的比较：对照组和实验组差异有 统计学意义（P <0.05）；节细胞- 神经母细胞瘤组和神经母细胞瘤组差异有统计学意义（P <0.05）；术前化 疗组和术前无化疗组差异有统计学意义（P <0.05）；Ⅲ期组和Ⅳ期组差异无统计学意义（P >0.05）；不同年龄、 性别差异无统计学意义（P >0.05）。表达呈正相关的是：C-Myc 和Sox2，C-Myc 和Oct4。呈负相关的是： C-Myc 和klf4，Sox2 和Klf4，Oct4 和Klf4。结论 C-Myc、Sox2、Oct4、Klf4 可能参与了儿童NB 的发生过 程；C-Myc、Oct4 和Klf4 与儿童NB 组织的分化程度相关，可能成为判断预后的指标；化疗药物对C-Myc、 Sox2、Oct4、Klf4 的表达有影响；Klf4 与C-Myc、Sox2、Oct4 在儿童NB 的发生、发展过程中相互拮抗发 挥作用；C-Myc、Sox2、Oct4、Klf4 在NB 组织中的表达与年龄、性别及临床分期无关。

Abstract:

Objective To investigate the role of stem cell transcription factors C-Myc, Sox2, Oct4 and Klf4 expressions, and their significance in the children’s neuroblastoma (NB). Methods The subjects of the children’s NB included 53 cases which were confirmed by pathological examination (NB group). The cases were divided into a stage III group, a stage IV group, a neuroblastoma group, a ganglioneuroblastoma group, a group without preoperative chemotherapy, and a group with preoperative chemotherapy. In addition, 10 cases of residual normal adrenal gland specimens, which were from the patients with severe hydronephrosis who received surgical resection, were used as the control group. Immunohistochemical SP method was employed to detect the expressions of C-Myc, Klf4, Oct4 and Sox2. The influence of chemotherapy on the expressions was analyzed. The correlations of the above four factors with clinical stage, pathological type, gender and age were analyzed. Results The positive expression rates of C-Myc, Sox2, Oct4 and Klf4 were significantly different between the control group and the NB group (P < 0.05),the ganglioneuroblastoma group and the neuroblastoma group, the group with preoperative chemotherapy and the group without preoperative chemotherapy (P < 0.05). There were no significant differences in the positive expression rates of C-Myc, Sox2, Oct4 or Klf4 between the stage Ⅲ and stage Ⅳ groups (P > 0.05) and among the patients with different age or genders (P > 0.05). The expression of C-Myc was positively correlated with Sox2 and Oct4. The expression of Klf4 was negatively correlated with C-Myc and, Sox2 and Oct4. Conclusions C-Myc, Sox2, Oct4 and Klf4 might participate in the occurrence of NB. C-Myc, Oct4 and Klf4 have correlations with the differential degree of NB tissues in children, and might become the prognostic indicators. The four factors are correlated with the mechanism of the chemotherapeutic drugs, and reflect the effect of chemotherapy. Klf4 and other three factors have antagonism effects in the development and progression of children’s NB. In NB tissues, none of C-Myc, Sox2, Oct4 and Klf4 expressions has relationship with age, gender or clinical stage.