线粒体DNA D-100p基因变异与肾透明细胞癌预后相关性分析

目的：探讨肾透明细胞癌患者线粒体DNAD-loop（mtDNAD-loop）基因变异的特点，以寻找新的判断肾透明细胞癌预后的标志。方法：对2002-08-01-2007-08-31河北医科大学第四医院59例完整随访的肾癌患者采用外周血基因组DNA，运用聚合酶链反应（PCR）对mtDNAD-loop区进行扩增并测序。将mtDNAD-loop区的测序结果与线粒体文库中的RevisedCambridgeReferenceSequence（rCRS）比对进行单核苷酸变异性分析。比较基因变异和临床随访资料与肾透明细胞癌预后的潜在关系，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5年生存率为67．5％（36／59），低于〈55岁组的85．0％（23／59），X^2=124．042，P〈0．001；男性5年生存率为71．7％（35／59），低于女性的78．5％（24／59），X^2=15．115，PG0．001；高TNM分期组患者5年生存率为72．5％（39／59），低于低TNM分期组的78．4％（20／59），X^2=11．123，P=0．001；肿瘤直径≥5cm患者生存率为68．3％（37／59），低于肿瘤直径〈5cm患者的84．6％（22／59），X^2=103．690，P〈0．001。mtDNAD-loop区测序结果显示，有12个分布频率〉5％的变异位点。262T和262C的5年生存率分别为70．4％和80．7％，差异有统计学意义，X^2=65．145，P〈0．001。多因素分析显示，TNM分期高低、肿瘤直径大小、262位点的变异是影响肾透明细胞癌患者预后的独立危险因素，P〈0．001。结论：分析肾透明细胞癌患者mtDNAD-loop区的变异可判断肾透明细胞癌患者的预后，其中262T可作为判断肾透明细胞癌患者预后的一个新型、独立的指标。

Relationship between gene variation in Mitochondrial Displacement-loop and the prognosis of clear cell renal cell carcinoma

OBJECTIVE： To investigate the relationship between gene variation in mitochondrial displacement-loop and the outcome of clear cell renal cell carcinoma （ccRCC） and find a novel prognositc factor. METHODS： Totally 59 ccRCC patients having complete follow-up information up to 5 years were included in the study. Genotype analysis was performed by polymerase chain reaction （PCR）. 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 SNP site. The main risk factors were screened by Cox hazard regression model. RESULTS： The 5-year suvival rate of patients with〈55 years （67.5%） was lower than that of patients with 〈55 years （85.0%,;X^2= 124. 042,P〈0. 001） ;the 5-year survival rate of male patients （71.7%） was lower than that of female patients （78.5%, X^2 = 15.115, P〈0. 001） ;the 5-year survival rate of patients with high TNM classification （72.5 %） was lower than that of patients with low TNM classification （78.4 %, X^2= 11. 123, P= 0. 001）;the 5-year survival rate of patients with tumor diameter ≥5 cm （68. 3%） was lower than that of patients with tumor diameter〈5 cm （84. 6%, X^2= 103. 690, P〈 0. 001） ,the 5-year survival rate of patients with 262T （70.4%） was lower than that of patients with 262C （80.7%, X^2 = 65. 145,P〈0. 001）. Multivariate analysis by the Cox proportional hazards model showed that TNM classification, tumor diameter and 262T were the independent risk factors for the eeRCC outcome. CONCLUSION.. Genetic variation in the D-loop are predictive markers for the outcome of clear cell renal cell carcinoma patients,262T is a novel independent prog- nostic marker for clear cell renal cell carcinoma.