心肌不同miRNA对于非小细胞肺癌患者应用贝伐单抗致相关心脏毒性的早期预警价值  

Early warning value of different myocardial microRNAs in patients with non-small cell lung cancer with bevacizumab-related cardiotoxicity

作　　者：文慧[1] 艾葆春 张兵兵 王倩如 李小峰[1] 郝光军[1] WEN Hui;AI Baochun;ZHANG Bingbing;WANG Qianru;LI Xiaofeng;HAO Guangjun(Department of Oncology Center,Yulin First Hospital,Shanxi Province,Yulin 719000,China)

机构地区：[1]陕西省榆林市第一医院肿瘤诊疗中心,719000

出　　处：《疑难病杂志》2018年第12期1347-1351,共5页Chinese Journal of Difficult and Complicated Cases

摘　　要：目的分析心肌不同miRNA(miR-1、miR-208和miR-30c)对于非小细胞肺癌患者应用贝伐单抗致相关心肌损伤的早期预警价值。方法纳入2016年1月—2018年4月于陕西省榆林市第一医院肿瘤诊疗中心住院治疗的NSCLC患者68例作为研究对象,其中出现心肌损伤19例为心肌损伤组,未出现心肌损伤49例为对照组。分别于入组时(T0)和治疗后6个月(T2)进行心脏超声检测,评价心脏功能。入组前(T0),入组后3个月(T1)和入组后6个月(T2)检测血清N末端B型脑钠肽前体(NT-proBNP),血清肌钙蛋白I(cTnI)以及心肌特异性miRNA(miR-1、miR-208和miR-30c)水平。结果 T2时心肌损伤组患者LVEDD水平较T0明显增加(t=6. 616,P <0. 001),而FS、LVEF和E/A水平均明显下降(t=2. 364,P=0. 012; t=9. 118,P <0. 001; t=3. 761,P <0. 001)。T2时心肌损伤组患者LVEDD水平明显高于对照组患者(t=5. 276,P <0. 001),而LVEF和E/A水平均明显低于对照组患者(t=9. 571,P <0. 001; t=3. 019,P=0. 002)。心肌损伤组患者NT-proBNP、miR-1、miR-208和miR-30c在T1和T2时均明显进行性上升(F/P=4. 445/0. 007,4. 199/0. 008,3. 809/0. 014,4. 063/0. 010);而对照组仅可见NT-proBNP和miR-208在T1时明显上升(F/P=4. 082/0. 010; 3. 289/0. 026)。心肌损伤组T1时NT-proBNP、miR-1和miR-30c均较对照组T1时明显升高(t=2. 016,P=0. 026; t=11. 230,P <0. 001; t=4. 582,P <0. 001),而心肌损伤组T2时NT-proBNP、miR-1、miR-208和miR-30c均较对照组T2时明显升高(t=25. 97,P <0. 001; t=24. 36,P <0. 001; t=15. 92,P <0. 001; t=15. 22,P <0. 001)。T1或△(△=T1-T0) NT-proBNP和miRNAs(miR-1、miR-208和miR-30c)对于早期预警贝伐单抗心肌损伤的AUC波动在0. 536～0. 901,其中△miR-1的AUC最高为0. 901,cut-off值为1 462. 3 fmol/L,敏感度90. 6%,特异度89. 3%,约登指数为0. 799。结论经贝伐单抗治疗1个月后miR-1的水平波动情况是早期预警贝伐单抗心肌损伤的潜在评价手段之一。Objective To analyze the early warning value of different myocardial microRNAs (miR-1,miR-208 and miR-30c) for myocardial injury induced by bevacizumab in patients with non-small cell lung cancer. Methods Sixty-eight NSCLC patients hospitalized in Tumor Diagnosis and Treatment Center of Yulin First Hospital of Shaanxi Province from January2016 to April 2018 were enrolled as the study subjects. Nineteen patients with myocardial injury were in the myocardial injury group,and 49 patients without myocardial injury were in the control group. Cardiac echocardiography was performed at admission (T0) and 6 months after treatment (T2) to evaluate cardiac function. Serum levels of N-terminal B-type natriuretic peptide precursor (NT-proBNP),serum troponin I (cTnI) and myocardial specific microRNAs (miR-1,miR-208 and miR-30 c)were measured before admission (T0),three months after admission (T1) and six months after admission (T2). Results At T2,the level of LVEDD in patients with myocardial injury was significantly higher than that of T0 (t = 6. 616,P <0. 001),while the levels of FS,LVEF and E/A were significantly decreased (t = 2. 364,P = 0. 012,t = 9. 118,P < 0. 001,t = 3. 761,P < 0. 001). The level of LVEDD in the myocardial injury group was significantly higher than that in the control group at T2 (t = 5. 276,P < 0. 001),while the LVEF and E/A levels were significantly lower than those in the control group (t = 9. 571,P < 0. 001,t = 3. 019,P = 0. 002). NT-proBNP,miR-1,miR-208 and miR-30 c in the myocardial injury group were significantly increased at T1 and T2 (F/P = 4. 445/0. 007,F/P = 4. 199/0. 008,F/P = 3. 809/0. 014,F/P = 4. 063/0. 010); Only NT-proBNP and miR-208 were seen to increase significantly at T1 (F/P = 4. 082/0. 010,F/P = 3. 289/0. 026). NT-proBNP,miR-1 and miR-30 c were significantly higher in T1 than in the control group (t = 2. 016,P = 0. 026,t = 11. 230,P < 0. 001,t = 4. 582,P < 0. 001),while myocardium NT-proBNP,miR-1,miR-208 and miR-30 c were significantly higher in the injury group than in the contro

关 键 词：非小细胞肺癌 微小RNA 贝伐单抗 心脏毒性 早期预警 

分 类 号：R734.2[医药卫生—肿瘤]