促血管生成miR与乳腺癌新辅助化疗心脏毒性的关联  

Correlation of Pro-angiogenic microRNA Expression Levels with Cardiotoxic Risks by Chemotherapy in Breast Cancer

作　　者：秦宪涛 支庆江[1] 王振峰[1] 姜文营 常方圆[2] QIN Xiantao;ZHI Qingjiang;WANG Zhenfeng;JIANG Wenying;CHANG Fangyuan(Department of General Surgery,The Second People’s Hospital of Liaocheng,Liaocheng 252600,China;Department of Cardiology,The Second People’s Hospital of Liaocheng,Liaocheng 252600,China)

机构地区：[1]聊城市第二人民医院华美院区综合外科,聊城252600 [2]聊城市第二人民医院心内科,聊城252600

出　　处：《福建医科大学学报》2019年第5期297-302,308,共7页Journal of Fujian Medical University

摘　　要：目的评估促血管生成microRNA(miR)水平与乳腺癌化疗心脏毒性发生风险的关联。方法纳入新辅助化疗的乳腺癌患者195例,于化疗前采集患者的血浆并采用qPCR检测14个促血管生成miR的水平,评估化疗期间及化疗后12月内心脏毒性的发生率。结果随访期间,共有11例(5.6%)患者发生心脏毒性。差异比较分析显示,基线血浆let-7f(P=0.027),miR-20a(P=0.008),miR-126(P=0.009),miR-210(P=0.048)和miR-378(P=0.043)的表达水平在发生心脏毒性患者中均显著降低。而采用单元和多元逻辑回归模型分析发现,基线let-7f(P=0.016),miR-20a(P=0.047),miR-126(P=0.025)和miR-210(P=0.041)是心脏毒性发生低风险的独立预测因素。进一步使用受试者工作曲线进行分析发现,联合let-7f,miR-20a,miR-126和miR-210表达水平对于心脏毒性发生低风险有着较强的预测价值,曲线下面积(AUC)为0.887,95%CI为0.809~0.965,在最佳工作点达到敏感度77.2%,特异度90.9%。此外,基线期(C0)血浆let-7f(P<0.001)和miR-20a(P=0.001)与乳腺癌心脏毒性标记物血浆cTnI水平呈现负相关。结论循环中let-7f,miR-20a,miR-126和miR-210的水平可以作为乳腺癌化疗心脏毒性低风险的生物标记物。Objective To assess the correlation of pro-angiogenic microRNA(miR)expressions with risks of cardiotoxicity by chemotherapy in breast cancer.Methods The prospective cohort study included 195 breast cancer patients who received neoadjuvant chemotherapy.Their plasma samples were collected before chemotherapy and were detected by qPCR for 14 pro-angiogenic miR.Incidence of cardiotoxicity was assessed during chemotherapy and within 12 months post chemotherapy.Results The cardiotoxicity occurred in total of 11 patients(5.6%).Baseline let-7f(P=0.027),miR-20a(P=0.008),miR-126(P=0.009),miR-210(P=0.048),and miR-378(P=0.043)were markedly declined in patients presented with cardiotoxicity.Univariate and multivariate logistic regressions revealed that let-7f(P=0.016),miR-20a(P=0.047),miR-126(P=0.025),and miR-210(P=0.041)were independent predictive factors for the occurrence of cardiotoxicity.Furthermore,the receiver operating characteristics curve illuminated that combining let-7f,miR-20a,mIR-126 and miR-210 had a good area under curve(AUC)of 0.887(95%CI:0.809-0.965),and the sensitivity as well as specificity at the best cut off point were 77.2%and 90.9%,respectively.In addition,baseline plasma let-7f and miR-20a expressions were negatively correlated with the cardiotoxicity biomarker cTnI level in breast cancer patients.Conclusion Circulating let-7f,miR-20a,miR-126 and miR-210 expressions could be served as biomarkers for predicting lower risks of cardiotoxicity by chemotherapy in patients with breast cancer.

关 键 词：乳腺肿瘤 化学疗法 辅助 微小RNA 心脏 

分 类 号：R322.11[医药卫生—人体解剖和组织胚胎学] R737.9[医药卫生—基础医学]