化疗前外周血lncRNAs表达水平对抗结核药物肝损伤的预测价值

Predictive value of lncRNAs expression level in peripheral blood before chemotherapy on anti-tuberculosis drug induced liver iniury

目的研究化疗前外周血长链非编码RNAs(lncRNAs)表达水平对抗结核药物肝损伤(ATDILI)的预测价值。方法选择2017年5月至2019年5月期间收治的初治肺结核患者,采用lncRNAs芯片及荧光定量PCR检测化疗前外周血中lncRNAs的表达水平,根据化疗期间是否发生ATDILI分为ATDILI组和非ATDILI组。采用ROC曲线分析lncRNAs对ATDILI的预测价值,采用logistic回归模型分析ATDILI的影响因素。结果经lncRNAs芯片分析,与非ATDILI组比较,ATDILI组外周血中共46种lncRNAs表达显著上调,其中上调倍数最大的5种lncRNAs为lncRNA MALAT1、HNF1α-AS1、H19、XIST、CCAT1;经荧光定量PCR检测,ATDILI组外周血中lncRNA MALAT1、HNF1α-AS1、XIST、CCAT1的表达水平显著高于非ATDILI组;经ROC曲线分析,lncRNA MALAT1、HNF1α-AS1、XIST、CCAT1对ATDILI具有预测价值;经logistic回归分析,性别、营养不良、病毒性肝炎史、饮酒史以及lncRNA MALAT1、XIST是ATDILI的影响因素。结论化疗前外周血lncRNA MALAT1、XIST表达增加与ATDILI的发生有关,可作为预测ATDILI的指标。

Objective To study the predictive value of long non-coding RNAs(lncrnas)expression in peripheral blood before chemotherapy on anti-tuberculosis drug induced liver iniury(ATDILI).Methods From May 2017 to may 2019,patients with newly diagnosed pulmonary tuberculosis in our hospital were selected,the expression level of lncRNAs in peripheral blood before chemotherapy were determined by lncRNAs microarray and fluorescence quantitative PCR.The patients were divided into ATDILI group and non-ATDILI group according to whether ATDILI occured during chemotherapy.ROC curve was used to analyze the predictive value of lncRNAs for ATDILI,and logistic regression model was used to analyze the influencing factors of ATDILI.Results By lncrnas microarray analysis,compared with non-ATDILI group,the expression of 46 lncRNAs in peripheral blood of ATDILI group significantly up-regulated and the 5 most upregulation lncRNAs were lncRNA MALAT1,HNF1α-AS1,H19,XIST and CCAT1.By fluorescence quantitative PCR,the expression of lncRNA MALAT1,HNF1α-AS1,XIST and CCAT1 in peripheral blood of ATDILI group were significantly higher than non-ATDILI group;ROC curve analysis showed that lncRNA MALAT1,HNF1α-AS1,XIST and CCAT1 had predictive value for ATDILI;logistic regression analysis showed that gender,malnutrition,viral hepatitis history,drinking history and lncRNA MALAT1,XIST were the influencing factors of ATDILI.Conclusion The increased expression of lncRNA MALAT1 and XIST in peripheral blood before chemotherapy relates to the occurrence of ATDILI,which can be used as a predictor for ATDILI.