内皮素-1基因多态性与贝伐单抗治疗转移性乳腺癌疗效相关性研究  

The Correlation Study of Endothelin-1 Genetic Polymorphism and Bevacizumab for Treatment of Metastasis Breast Cancer Patients

作　　者：张丹峰[1,2] 王曼 张华[1] 王耕[1] 王明华[1] 蔡晓军[3] ZHANG Danfeng;WANG Man;ZHANG Hua;WANG Geng;WANG Minghua;CAI Xiaojun(Department of Endocrinology, Taihe Hospital of Shiyan City, Shiyan, Hubei, 442000, China;Graduate School of Peking Union Medical College, Beijing, 100050, China;Department of Oncology, Shiyan People’s Hospital, Shiyan, Hubei, 442000,China)

机构地区：[1]十堰市太和医院内分泌血管外科,湖北十堰442000 [2]北京协和医学院研究生院,北京100050 [3]十堰市人民医院肿瘤科,湖北十堰442000

出　　处：《肿瘤药学》2017年第5期562-567,共6页Anti-Tumor Pharmacy

基　　金：国家自然科学基金项目(81272698)

摘　　要：目的探讨血管内皮生长因子-A(VEGF-A)、血管内皮生长因子受体-1(VEGFR-1)、丝氨酸/苏氨酸激酶39(STK39)、内皮素-1(EDN1)和尿调素基因多态性对化疗联合贝伐单抗治疗转移性乳腺癌(MBC)患者的疗效和不良反应的相关性。方法选取在我院治疗的516例MBC患者,人表皮生长因子受体-2(HER2)均为阴性。根据是否使用贝伐单抗将患者分为对照组(单纯化疗)和贝伐单抗组(化疗+贝伐单抗),每组各258例。提取患者肿瘤组织或血液样本DNA进行分析。采用Kaplan–Meier法评估不同基因型患者的生存曲线,采用Cox比例风险回归评估等位基因变异与无进展生存期(PFS)、总生存期(OS)的相关性。结果与其他基因携带者比较,贝伐单抗组携带EDN1基因rs5370-TT单核苷酸多态性患者中位OS显著降低(6.2 vs.21.4个月,HR=2.88,95%CI:1.35~6.27,P=0.007),中位PFS降低,但差异无统计学意义(3.4 vs.7.8个月,HR=2.05,95%CI:0.97~4.40,P=0.066)。与VEGF-936 CC或CT基因携带者比较,VEGF-936(rs3025039)TT基因携带者中位OS显著降低(14.8 vs.21.4个月,HR=2.38,95%CI:1.09~5.13,P=0.029)。多变量分析显示,EDN1与OS显著相关(P=0.013)。对照组患者EDN1基因与生存率不相关。结论 EDN1基因遗传变异对MBC含贝伐单抗治疗方案的疗效有显著影响。Objective To examine the impact of gene polymorphisms in vascular endothelial growth factor-A(VEGF-A),VEGF receptor1(VEGFR-1),serine threonine kinase39(STK39),endothelin-1(EDN1)and uromodulin on the efficacy and toxicity of bevacizumabin combination with chemotherapy in patients with metastatic breast cancer(MBC).Methods For this biomarker study,DNA was extractedfrom tumor blocks or blood samples of patients with human epidermal growth factor receptor2(HER2)-negative MBC treated with bevacizumabin combination with chemotherapy(bevacizumab group,163patients)or chemotherapy only(control group,105patients).ResultsCompared with other gene carriers,the patients of the bevacizumab group carrying the EDN1gene rs5370-TT single nucleotide polymorphisms(SNP)with OS median(6.2months vs.21.4months,HR=2.88,95%CI:1.35~6.27,P=0.007)significantly reduced,PFS decreasedtoo,but the difference was not statistically significant(3.4months vs.7.8months,HR=2.05,95%CI:0.97～4.40,P=0.066).Compared withVEGF-936CC or CT gene carriers,the median OS was significantly decreased in VEGF-936(rs3025039)TT gene carriers(14.8months vs.21.4months,HR=2.38,95%CI:1.09～5.13,P=0.029).Multivariate analysis showed that EDN1was significantly associated with OS(P=0.013).In the control group,the EDN1gene was not associated with patient survival.Conclusion Genetic variation of EDN1gene hasa significant effect on the efficacy of bevacizumab for the treatment of MBC,and the role of clear EDN1beneficial to bevacizumab on breastcancer treatment.

关 键 词：转移性乳腺癌 内皮素-1基因多态性 贝伐单抗 化疗 

分 类 号：R737.9[医药卫生—肿瘤]