CAJ | 학술논문

目的：探讨人不同病理级别脑胶质瘤组织中 RWD 结构修饰增强子(RWD containing sumoylation enhancer, RSUME)、泛素样小分子修饰因子(small ubiquitin-like modifier,SUMO)-1、缺氧诱导因子-1α(hypoxia inducible factor-1α)、血管内皮生长因子(VEGF)的表达及其相关性。方法应用 RT-PCR 法检测63例不同级别人脑胶质瘤组织及9例正常脑组织中 RSUME mRNA、HIF-1αmRNA、VEGF mRNA 的表达,免疫组化检测组织中 SUMO-1、HIF-1α、VEGF 表达情况,分析与胶质瘤分级的关系以及表达的相关性。结果脑胶质瘤组织中 RSUME、HIF-1α、VEGF mRNA 较正常脑组织中表达明显增高(P <0.01),并随胶质瘤恶性程度的增高而表达增高(P <0.01),RSUME 与HIF-1α、VEGF 的 mRNA 表达水平呈正相关；脑胶质瘤组织中 SUMO-1、HIF-1α、VEGF 的蛋白表达较正常脑组织明显增高(P <0.01),并随胶质瘤恶性程度的增高而表达增高(P <0.01),SUMO-1与 HIF-1α蛋白表达呈正相关(r =0.857,P <0.01)；Kaplan-Meier 生存分析及 Log-rank 检验显示低表达 RSUME 患者的 PFS 明显长于高表达组(χ2=36.032,P <0.01)。结论RSUME 可能通过 SUMO 化增强 HIF-1α/VEGF 通路表达,预示 RSUME 可能与脑胶质瘤血管新生及肿瘤的侵袭、进展有关,预示 RSUME 可作为胶质瘤治疗的新靶点。
목적：탐토인불동병리급별뇌효질류조직중 RWD 결구수식증강자(RWD containing sumoylation enhancer, RSUME)、범소양소분자수식인자(small ubiquitin-like modifier,SUMO)-1、결양유도인자-1α(hypoxia inducible factor-1α)、혈관내피생장인자(VEGF)적표체급기상관성。방법응용 RT-PCR 법검측63례불동급별인뇌효질류조직급9례정상뇌조직중 RSUME mRNA、HIF-1αmRNA、VEGF mRNA 적표체,면역조화검측조직중 SUMO-1、HIF-1α、VEGF 표체정황,분석여효질류분급적관계이급표체적상관성。결과뇌효질류조직중 RSUME、HIF-1α、VEGF mRNA 교정상뇌조직중표체명현증고(P <0.01),병수효질류악성정도적증고이표체증고(P <0.01),RSUME 여HIF-1α、VEGF 적 mRNA 표체수평정정상관；뇌효질류조직중 SUMO-1、HIF-1α、VEGF 적단백표체교정상뇌조직명현증고(P <0.01),병수효질류악성정도적증고이표체증고(P <0.01),SUMO-1여 HIF-1α단백표체정정상관(r =0.857,P <0.01)；Kaplan-Meier 생존분석급 Log-rank 검험현시저표체 RSUME 환자적 PFS 명현장우고표체조(χ2=36.032,P <0.01)。결론RSUME 가능통과 SUMO 화증강 HIF-1α/VEGF 통로표체,예시 RSUME 가능여뇌효질류혈관신생급종류적침습、진전유관,예시 RSUME 가작위효질류치료적신파점。
Objective To explore the expressions and correlation of RWD containing sumoylation enhancer (RSUME),small ubiquitin-like modifier (SUMO-1),hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor (VEGF)in gliomas of different pathologic grade.Methods We investigated the expression levels of RSUME mRNA,HIF-1α mRNA and VEGF mRNA with reverse transcription-polymerase chain reaction (RT-PCR),and investigated the immunohistochemical staining to determine the expressions of SUMO-1,HIF-1α and VEGF in 63 cases of human gliomas of different pathologic grade and 9 cases of normal brain tissues.We studied its correlation with the pathologic grade and the relationship between the expression of RSUME promoter sumoylation and HIF-1α/VEGF pathway in gliomas.Results There were significant differences (P <0.01)in the expressions of RSUME mRNA,HIF-1αmRNA and VEGF mRNA in glioma tissues.With the increasing degree of pathologic grade in tumor specimens,the expression levels of RSUME mRNA,HIF-1α mRNA and VEGF mRNA increased markedly (P <0.01 ).There was a positive correlation of the expression levels of RSUME mRNA with HIF-1αmRNA and VEGF mRNA.There were significant differences (P <0.01 )in the expressions of SUMO-1,HIF-1αand VEGF in glioma tissues by immunohistochemical staining.With the ascending of pathologic grade of tumor specimens,the expression levels of SUMO-1,HIF-1α and VEGF increased markedly (P < 0.01 ).There was a positive correlation between the expression level of SUMO-1 and HIF-1α(r =0.857,P <0.01).The Kaplan-Meier analysis and Log-rank test showed significant differences in progress free survival (PFS)between the RSUME high-expression and low-expression groups (χ2 =36.032,P <0.01).Conclusion RSUME may enhance HIF-1α/VEGF pathway through sumoylation in gliomas.It implicates that RSUME is related to angiogenesis in gliomas and can promote tumor invasion and progression,indicating that RSUME can be a novel target in gliomas treatment.