Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.
目的 探讨硒蛋白基因在人类免疫缺陷病毒(HIV)感染及其母婴传播中的表达水平,为艾滋病的预防及诊疗提供新的理论依据。方法 在基因表达数据库检索下载数据集GSE4124,样本由HIV阳性组(n=25)和对照组(n=20)构成,其中HIV阳性组包括母婴传播(TR)组(n=11)和非母婴传播(NTR)组(n=14);采用t检验分析4组(HIV阳性组比对照组、NTR组比对照组、TR组比对照组、TR组比NTR组)硒蛋白基因表达水平的差异;随后采用单因素和多因素Logistic回归分析差异表达基因对HIV感染和母婴传播的影响;应用R语言构建列线图预测模型并验证其效能。结果 与对照组比较,HIV阳性组、NTR组、TR组分别有8、5、8个差异表达硒蛋白基因为下调基因;与NTR组比较,TR组有4个差异表达硒蛋白基因为下调基因。单因素Logistic回归分析显示,GPX1、 GPX3、 GPX4、 TXNRD1、TXNRD3、 SEPHS2基因异常高表达对HIV感染均具有影响,而对母婴传播无影响作用。多因素Logistic回归分析显示,TXNRD3基因的异常高表达与是否HIV感染呈正相关(OR=0.032,95%CI= 0.002~0.607,P =0.022)。列线图预测模型的预测效能显示,HIV感染者生存时间1、3年的受试者工作特征曲线下面积分别为0.840(95%CI=0.690~1.000)和0.870(95%CI=0.730~1.000)。结论 多个硒蛋白基因差异表达水平下调,参与调控HIV感染和母婴传播过程;其中,TXNRD3基因异常高表达与是否HIV感染呈正相关,为艾滋病防治、诊疗提供了新思路。.
Keywords: Logistic regression; human immunodeficiency virus; mother-to-child transmission; nomogram; selenoprotein gene.