肾透明细胞癌线粒体DNA非D-loop区微卫星不稳定性与预后的关系  

Relationship between microsatellite instability in non-displacement-loop region of mitochondrial DNA and the outcome of clear cell renal cell carcinoma

作　　者：耿同会[1] 徐金升[1] 白亚玲[1] 张俊霞[1] 崔立文[1] 张慧然[1] 张胜雷[1] 

机构地区：[1]河北医科大学第四医院肾内科,河北石家庄050011

出　　处：《中华肿瘤防治杂志》2016年第1期21-24,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：河北省科技计划(122777219)

摘　　要：目的线粒体DNA（mitochondrial DNA，mtDNA）是多种肿瘤的热点变异区域，其中线粒体微卫星不稳定性（mitochondrial microsatellite instability,mtMSI）与肿瘤相关。本研究探讨肾透明细胞癌（clear cell renal cell carcinoma,ccRCC）患者mtDNA非D-环（displacementloop，D-loop）的微卫星不稳定性（microsatellite instability, MSI）与ccRCC患者预后的关系，以寻找新的判断ccRCC预后的标志物。方法采集河北医科大学第四医院2002-08—01—2007—08—31随访资料完整的70例肾癌患者外周血，并提取基因组DNA，运用聚合酶链反应（PCR）对mtDNA非D-loop区的3个微卫星灶5892-5919、8272-8289和9777-9782进行扩增并测序。将mtDNA非D-loop区的测序结果与线粒体文库中的剑桥序列（revisedcambridgereferencesequence，rCRS）进行比对，以判断该区域的微卫星状态，分析mtMSI和临床随访资料与ecRCC预后的潜在关系。生存曲线分析采用Kaplan-Meier方法，组间比较采用Log-rank检验，多因素分析采用Cox比例风险回归模型。结果影响肾透明细胞癌患者5年生存率的单因素分析显示，〉55岁组患者的5年生存率低于≤55岁组，χ2=135．213，P〈0．001；男性组的5年生存率低于女性组，χ2=7．850，P=0．005；肿瘤直径≥5cm组低于〈5cm组，χ2=43．202，P〈0．001；透明细胞癌组低于非透明细胞癌组，χ2=49．273，P〈0．001；线粒体DNA8272—8289区域9bp正常组（CCCCCTCTACCCCCTCTA）高于9bp缺失组（CCCCCTCTA），χ2=39．216，P〈0．001；5892-5919和9777—9782区域的MSI与患者5年生存率差异无统计学意义，χ2值分别为1．117和4．011，P值分别为0．291和0．527。多因素分析显示，肿瘤直径大小、病理类型和8272—8289区域的MsI是影响ceRCC患者预后的独立危险因素。结论肿瘤直径大小、病理类型是影响ccRCC患者预后的独立危险因素。分析ccRCC患者mtDNA非D-loop区的MSI，可判断ccRCC患者的预�OBJECTIVE Mitochondrial DNA （mtDNA） is considered a mutation hotspot in various types of tumors, and mitochondrial DNA microsatellite instability （mtMSI） is associated with various cancers. To investigate the relationship between microsatellite instability in mitochondrial non-displacement-loop and the outcome of clear cell renal cell carcinoma （ccRCC） and find a novel prognostic marker for ccRCC patients. METHODS Totally 70 ccRCC patients, who were all in the Fourth Hospital of Hebei Medical University between 8/1/2002 and 8/31/2007 and had completed fol- low-up information up to 5 years,were included in the study. MSIs （5892-5919,8272-8289,9777-9782） analysis was per- formed using polymerase chain reaction （PCR） and cyclic cycle sequencing. The analysis of association of ccRCC outcome with the genetic variation and follow-up data was performed. The survival curve was calculated with the Kaplan-Meier method and compared by the Log-rank test at each MSI site. The main risk factors were screened by Cox hazard regres- sion model. RESULTS The 5-year survival rate of patients with ≥ 55 years was lower than that of patients with 〈55 years （χ2= 135. 213, P〈0. 001）; the 5-year survival rate of male patients was lower than that of female patients（χ2= 7. 850,P= 0. 005）; the 5-year survival rate of patients with tumor diameter≥5 cm was lower than that of patients with tumor diameter〈5cm （χ2 =43. 202 ,P〈0. 001） ; the 5-year survival rate of patients with clear cell renal cell carcino- ma was lower than that of patients with non-clear cell renal cell carcinoma （χ2= 49. 273,P〈0. 001）; the 5-year survival rate of patients with 8272-8289 CCCCCTCTA CCCCCTCTA was higher than that of patients with 8272-8289 CCCCCTC- TA （X2=39. 216,P〈0. 001）,but no significant correlation was found between the MSIs of 5892-5919 （χ2 =1. 117,P= 0. 291） and 9777 9782 （χ2 =4. 011,P=0. 527） and the 5-year survival rate of patients. Multivariate analysis by the Cox proportional hazards

关 键 词：肾透明细胞癌 PCR 线粒体DNA 微卫星不稳定性 预后 

分 类 号：R737.11[医药卫生—肿瘤]