Identification and Analysis of Hub Transcriptional Factors in vitro hepatocyte model of Acetaminophen- Induced Liver Injury

Abstract

Abstract Background Acetaminophen-induced liver injury (AILI) is one of the most common causes of acute liver failure. It becomes more recognized that Transcription factors are involved in morphology alterations of hepatocyte in AILI patients. The integrated analysis of the Transcription factors role in the pathogenesis in AILI remains unknown. Material and Methods Based on bioinformatics, GEO databases and TF databases,we identify and analyze the hub TFs in vitro hepatocyte model of 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, qRT-PCR showed that the expressions level 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 level 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).