MCD biomarkers Egfr, Hmox1, Lgmn identified in NAFLD.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic cell death (MCD), and this study aimed to dig deeper into the biomarkers associated with MCD in NAFLD, and to provide new references for the diagnosis and treatment of NAFLD.

Methods: The datasets and MCD-related genes (MCD-RGs) associated with NAFLD were downloaded from the Gene Expression Omnibus (GEO) database and the literature, respectively. Differentially expressed genes (DEGs) between NAFLD and control groups were identified and intersected with MCD-RGs to yield candidate genes. Biomarkers were obtained by screening under four machine learning models, Receiver Operating Characteristic (ROC) curves, and expression validation. Based on the biomarkers, functional enrichment, diagnostic model construction, network modulation, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed. At the same time, differential infiltration of immune cells in the NAFLD and control groups was analysed.

Results: The 17 candidate genes were mostly involved in processes such as immunity and apoptosis. After screening, Egfr, Hmox1, and Lgmn were identified as biomarkers. Among these, Egfr was down-regulated whereas Hmox1 and Lgmn were up-regulated in NAFLD. Based on these biomarkers, a nomogram diagnostic model was constructed and demonstrated excellent predictive performance (AUC = 0.997). Subsequent enrichment analyses showed enrichment in inflammatory regulation between biomarkers and NAFLD groups. In addition, in the TF-biomarker network, Egfr and Hmox1 co-predicted NF-κB1. SORAFENIB was co-predicted in drug prediction. Meanwhile, five differentially infiltrating immune cells, such as CD8 T cells, were found to be strongly negatively correlated (cor = -0.475) with Egfr in both the NAFLD and control groups.

Conclusion: In this study, Egfr, Hmox1, and Lgmn were used as biomarkers showing transcriptomic correlation with with MCD in NAFLD, and an excellent nomogram diagnostic model was developed accordingly, which is expected to provide a practical tool for diagnosis and treatment of NAFLD.

Clinical trial number: Not applicable.