Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the major seeds of liver cirrhosis and hepatocellular carcinoma. There is no convenient reliable non-invasive early diagnostic tool available for NAFLD/NASH diagnosis and stratification. Recently, the role of cytosolic sensor, stimulator of interferon genes (STING) signaling pathway in pathogenesis of nonalcoholic steatohepatitis (NASH) has been evidenced in research. We have selected EDN1/TNF/MAPK3/EP300/hsa-miR-6888-5p/lncRNA RABGAP1L-DT-206 RNA panel from bioinformatics microarrays databases related to STING pathway and NAFLD/NASH pathogenesis. We have used reverse-transcriptase real-time polymerase chain reaction to assess the expression of the serum RNAs panel in NAFLD/NASH without suspicion of advanced fibrosis, NAFLD/with NASH patients with suspicion of advanced fibrosis and controls. Additionally, we have assessed the diagnostic performance of the Ribonucleic acid (RNA) panel. We have detected upregulation of the EDN1 regulating RNAs panel expression in NAFLD/NASH cases compared to healthy controls. We concluded that this circulatory RNA panel could enable us to discriminate NAFLD/NASH cases from controls, and also NAFLD/NASH cases (F1, F2) from advanced fibrosis stages (F3, F4).
Highlights
Liver diseases cause two million deaths per year worldwide; they represent a universal health problem [1]
Key genes EDN1, E1A Binding Protein P300 (EP300), Mitogen-activated protein kinase 3 (MAPK3), and TNF were selected for the targeted network and validated by other GEO datasets (Supplementary Figure S1A,B) and other public databases to be related to stimulator of interferon genes (STING) signaling, cytokine response, and Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) pathogenesis (Supplementary Figures S2 and S3)
Discussion based on the involvement of STING pathway in NAFLD progression and NASH development, we constructed an mRNA/miRNA/lncRNA regulatory Ribonucleic acid (RNA) net‐ work linked to hepatocytes/macrophage/cytokine cross talk via in silico data analysis
Summary
Liver diseases cause two million deaths per year worldwide; they represent a universal health problem [1]. Nonalcoholic fatty liver disease (NAFLD) is a progressive chronic liver disease characterized by excess fat accumulation in the liver. NAFLD can progress to nonalcoholic steatohepatitis (NASH) and, eventually, liver cirrhosis and hepatocellular carcinoma (HCC) worldwide [2]. There are new promising predictors of NAFLD as combination of serum biomarkers that could help in early NASH diagnosis, but, with several well-known limitations. Magnetic resonance imaging-derived proton density fat fraction is considered the most accurate for fatty liver diagnosis. The main concern in clinical practice is early detection of NASH [3]
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