肾母细胞瘤中Stat3HIF-1α及VEGF的表达及意义

Expression of Stat3, HIF-1α and VEGF in Wilms' tumor

摘要:

目的：研究血管内皮生长因子(vascular endothelial growth factor, VEGF)，信号传导与转录激活因子3（signal transducer and activator of transcription 3，Stat3）和低氧诱导因子HIF-1α(hypoxia-inducible factor-1α, HIF-1α)在肾母细胞瘤(Wilms’ tumor, WT)中的表达及其临床意义。方法：应用免疫组化SABC法辅以计算机图像分析的方法，研究Stat3，HIF-1α与VEGF在52例WT组织，47例瘤旁组织及8例正常肾组织表达强度情况。结果：VEGF，Stat3及HIF-1α在WT组织中表达强度较瘤旁组织及正常肾组织显著增强(P<0.05)，且瘤旁组织中VEGF表达强度高于正常肾组织。另外，临床分期Ⅲ～Ⅳ和预后不良病理类型的WT中Stat3及VEGF表达强度明显高于临床分期Ⅰ～Ⅱ的WT， 预后不良病理类型及直径≥6 cm的WT中HIF-1α表达强度较预后良好型及直径<6 cm的WT升高。结论：VEGF，Stat3及HIF-1α表达与肾母细胞瘤的发展预后有关，参与了肿瘤血管的生成及肿瘤的增殖侵袭，Stat3可能对HIF-1和VEGF的表达起着重要的调控作用，对于靶向治疗肾母细胞瘤具有一定意义。［中国当代儿科杂志，2007，9（5）：461-464］

Abstract:

OBJECTIVE: To study the expression of signal transducer and activator of transcription 3 (Stat3), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in Wilms' tumor and their roles in the development of Wilms' tumor. METHODS: The expression of Stat3, HIF-1α and VEGF were detected by the immunohistochemical staining in 52 specimens from Wilms' tumor tissues, 47 from adjacent kidney tissues and 8 from normal kidney tissues. The expression intensity was analyzed by computer image processing. RESULTS:The expression of Stat3, HIF-1 and VEGF were significantly up-regulated in Wilms' tumor tissues compared to those in adjacent tissues and normal kidney tissues (P< 0.05). Stat3 and VEGF proteins in Wilms' tumor tissues of stage III-IV and high risk histopathology were significantly higher than those of stage I-II and low risk histopathology. The higher expression of HIF-1 in Wilms' tumor tissues was shown in tumors with high risk histopathology and tumor size ≥ 6 cm. CONCLUSIONS: Increased expression of Stat3, HIF-1 and VEGF were found in Wilms' tumor tissues, and may be related to the development and angiogenesis of Wilms' tumor. Stat3 may regulate the expression of HIF-1 and VEGF, so it could be an effective target for inhibiting VEGF expression and angiogenesis of Wilms' tumor.