摘要
目的探讨质谱多反应监测技术(multiple reaction monitoring-mass spectrometry,MRM-MS)对先天性心脏畸形(congenital heart diseases,CHD)蛋白标志物的筛查价值。方法 CHD胎儿孕妇30例为CHD组,正常胎儿孕妇20例为对照组,分别采用MRM-MS法及ELISA法检测2组血清LMNA、TPM4、MYH9、TLN1、APOC1、PF4V1、SAA4和HP蛋白表达水平,Pearson法分析ELISA法与MRM-MS定量检测结果的相关性,ROC曲线评估候选蛋白标志物诊断CHD的效能。结果MRM-MS定量检测CHD组血清LMNA[(0.18±0.16)fmol/mL]、TPM4[(0.94±0.46)fmol/mL]水平低于对照组[(0.30±0.19)、(1.56±0.88)fmol/mL](P<0.05),APOC1[(33.89±13.65)fmol/mL]高于对照组[(22.81±10.49)fmol/mL](P<0.05),MYH9、TLN1、PF4V1、HP、SAA4表达水平与对照组比较差异均无统计学意义(P>0.05);血清LMNA以0.14fmol/mL为最佳截断值,诊断CHD的AUC为0.800(95%CI:0.662~0.938,P<0.001),准确率为78.6%,灵敏度为100.0%,特异度为54.5%;血清TPM4以0.87fmol/mL为最佳截断值,诊断CHD的AUC为0.752(95%CI:0.601~0.904,P=0.001),准确率为73.8%,灵敏度为90.0%,特异度为54.6%;血清APOC1以22.8fmol/mL为最佳截断值,诊断CHD的AUC为0.777(95%CI:0.621~0.933,P<0.001),准确率为81.0%,灵敏度为80.0%,特异度为81.8%;LMNA、TPM4、APOC1分别以0.80、0.79、67.78fmol/mL为最佳截断值时,3种蛋白联合诊断CHD的准确率最高(88.1%),灵敏度为85.0%,特异度为90.9%;Pearson相关分析结果显示,MRM-MS定量与ELISA检测的LMNA、TPM4、APOC1蛋白水平均呈正相关(r=0.74,P=0.002;r=0.75,P=0.001;r=0.78,P=0.001)。结论 MRM-MS定量技术可获得LMNA、TPM4、APOC1 3种蛋白分子标志物,其联合诊断CHD具有较高的准确率。
Objective To explore the value of multiple reaction monitoring-mass spectrometry （MRM MS） to the screening of the protein markers for congenital heart disease （CHD）, Methods The expressions of LMNA, TPM4, MYH9, TLN1, APOC1, PF4V1, SAA4 and HP proteins were detected by MRM MS and EI.ISA technique in 30 pregnant women with CHD fetuses （CHD group） and 20 women with normal fetuses （control group）. Pearson analysis was used to evaluate the correlation between ELISA test results and quantitative MRM-MS results. The diagnostic efficiency of theses candidate protein markers for CHD was evaluated by ROC. Results MRM-MS results showed that serum LMNA and TPM4 concentrations were significantly lower in CHD group （（0. 18±0. 16）, （0. 94±0. 46） fmol/mL） than those in control group （ （0.30± 0.19）, （ 1.56 ±0.88） fmol/mL） （P〈 0.05 ）, while APOC1 concentration was significantly higher in CHD group （（33. 89--13. 65） fmol/mL） than that in control group （（22. 81± 10. 49） fmol/mL） （P〈0.05）. There were no significant differences in the expressions of MYH9, TLN1, PF4V1, HP and SAA4 between two groups （P〉0.05）. When the optimal cut-off value of serum LMNA was 0.14 fmol/mL, the AUC for the diagnosis of CHD was 0. 800 （95~CI： 0. 662-0. 938, P〈0. 001）, the accuracy was 78.6%, the sensitivity was 100.0% and the specificity was 54.5%. When the optimal cut-off value of serum TPM4 was 0.87 fmol/mL, the AUC for the diagnosis of CHD was 0. 752 （95%CI： 0. 601-0. 904, P=0. 001）, the accuracy was 73.8%, the sensitivity was 90.0% and the specificity was 54.6%. When the optimal cut-off value of serum APOC1 was 22.8 fmol/mL, the AUC for the diagnosis of CHD was 0. 777 （95%CI： 0. 621-0. 933, P〈0. 001）, the accuracy was 81.0%, the sensitivity was 80.0% and the specificity was 81.8%. When the optimal cut-off value of LMNA, TPM4 and APOC1 was 0.80, 0.79 and 67.78 fmol/mL respectively, the accuracy the joint detection for the diagnosis of CHD was the highest （88.1%）, the sensitivity was 85.0%, and the specificity was 90. 90/00. Pearson correlation analysis showed that LMNA, TPM4 and APOC1 protein levels detected by quantitative MRM-MS were positively correlated with those detected by ELISA （r= 0.74, P= 0. 002 ; r= 0.75, P= 0. 001 ~ r= 0.78, P= 0. 001 ）. Conclusion Quantitative MRM-MS can acquire three molecular markers as LMNA, TPM4 and APOC1 protein, and the joint diagnosis of them has high accuracy for CHD.
出处
《中华实用诊断与治疗杂志》
2018年第1期14-17,共4页
Journal of Chinese Practical Diagnosis and Therapy
基金
国家自然科学基金(81600258)
国家自然科学基金(81671469)
关键词
先天性心脏畸形
产前诊断
质谱多反应监测技术
血清标志物
Congenital heart dissease
prenatal diagnosis
multiple reaction monitoring-mass spectrometry
serum biomarker
