همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Novel Potential Peripheral ECM Biomarkers for Prognosis and Therapeutic Approaches in Liver Cirrhosis Based on Microarray Analysis

نویسندگان :

Sorour Akrami¹ Masoud Vosough²

1- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran 2- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran

کلمات کلیدی :

Biomarker،Liver Cirrhosis،Hub Gene،PPI network

چکیده :

Liver cirrhosis is a significant global health concern, with incident cases rising by 16.7% from 2009 to 2019 and contributing to nearly 1.5 million deaths globally by 2019 (Lan et al., 2023). Its pathogenesis involves excessive collagen deposition and extracellular matrix accumulation, leading to hepatocellular dysfunction and portal hypertension. Consequently, the identification of reliable biomarkers for diagnosis and prognosis has become paramount in clinical research (Ismaiel et al., 2024). To address this urgent need, we utilized microarray analysis to examine gene expression profiles and identify differentially expressed genes (DEGs) associated with disease progression. Dataset GSE97083, obtained from the Geo database, includes 10 male Wistar rat liver tissue samples, five normal control livers, and five cirrhotic liver models with DEN/TAA treatment (Romualdo et al., 2017). GEO2R analysis confirmed dataset normalization, and DEGs were screened based on adjusted P-value < 0.05 and |logFC| ≥ 1. A Protein-Protein Interaction Network of DEGs was constructed using the STRING database, beside Cytoscape software identified 12 hub genes (Agxt, Plg, Apoa5, Vtn, Akr1c6, Slc27a5, Serpinc1, Lipc, Lcat, Hrg, Pon1, Mbl1) based on betweenness centrality (BC), closeness centrality (CC), eigenvector centrality (EGC), and degree centrality (DC). Expression locations of the hub genes were identified using UniProt and DAVID databases, with genes expressing intracellularly excluded. Based on literature review, from the eight genes with secreted products to ECM and expression in liver cells reported by Enrichr, a panel of four genes—Plg, Apoa5, Mbl1, and Serpinc1—was suggested as putative diagnostic and prognostic biomarkers for liver cirrhosis and potential therapeutic targets to mitigate its pathological features. The plasminogen (Plg) gene may be involved in processes related to liver cirrhosis and hepatocellular carcinoma (HCC). Overexpression in HBV-induced HCC is hypothesized to promote tumor progression via the Hippo signaling pathway through SRC activation (Hu et al., 2021). The Apolipoprotein A5 )Apoa5( gene, which is primarily associated with triglyceride metabolism, may enhance triglyceride hydrolysis and remnant lipoprotein clearance in plasma. Its intracellular role could potentially contribute to triglyceride-rich lipid droplet accumulation, aggravating non-alcoholic fatty liver disease (NAFLD) (Ress et al., 2011; Forte and Ryan, 2015). Elevated Apoa5 expression is suggested to correlate with hepatic triglyceride storage in human and rat NAFLD livers (Feng et al., 2015). The Mannose-Binding Lectin (MBL) gene may play a role in immune defense and complement activation via the lectin pathway (Lo, Austin and Freeman, 2018). Mutations in the MBL gene, particularly at codon 54, are thought to be associated with the progression of chronic hepatitis B and increased risks of cirrhosis and spontaneous bacterial peritonitis (Yuen et al., 1999). Lastly, the Serpin family C member 1 (Serpinc1) gene is hypothesized to play a crucial role in regulating blood coagulation, modulating inflammatory responses, and maintaining vascular integrity, which may collectively influence hemostasis and fibrosis. Its potential role in platelet activity and cellular interactions suggests it could be significant in managing complications such as coagulopathy and variceal bleeding in cirrhotic patients (Kademani, Subramanian and Nelaturi, 2024; Pontisso and Parola, 2024).