Identification and Analysis of Hub Transcriptional Factors Related to Acetaminophen-Induced Liver Injury

Abstract

Abstract Background Acetaminophen-induced liver injury (AILI) is one of the most common causes of acute liver failure, and its pathogenesis remains unclear and there is a lack of effective early diagnostic markers. Material and Methods Based on bioinformatics , GEO databases and TF databases，we identify and analyze the hub TFs in AILI and further evaluate the value of these TFs in the early diagnosis of AILI. Results A total of 97 AILI-related differentially expressed transcriptional factors (DETFs) were obtained, which were mainly enriched in the transcriptional activity, rhythmic process, cell fate commitment, liver development, and hepaticobiliary system development. Ten hub TFs (MYC, TP53, CEBPB, FOXM1, E2F1, EGR2, FOSL1, JUND, E2F7 and E2F8) were obtained from the PPI networks. In the early stage of AILI, the expressions of MYC, TP53, CEBPB, E2F1, JUND, and E2F7 significantly changed compared with the control group (all P<0.05), and these hub TFs had high sensitivity and specificity(all AUC ≥0.9); in contrast, the expressions of FOXM1, EGR2, FOSL1 and E2F8 were not significantly different from those in the control group (all P＞0.05), and these hub TFs had certain sensitivity and specificity(all 0.67 ≤AUC≤0.79). Conclusions Ten hub TFs (MYC, TP53, CEBPB, FOXM1, E2F1, EGR2, FOSL1, JUND, E2F7 and E2F8) are closely related to AILI, among which MYC, TP53, CEBPB, E2F1, JUND, and E2F7 have better diagnostic performance for AILI in its early stages. These findings further understand the pathogenesis of AILI and provide new diagnostic markers for the early diagnosis of AILI.