New insights into potential biomarkers and their roles in biological processes associated with hepatitis C-related liver cirrhosis by hepatic RNA-seq-based transcriptome profiling

•Hepatic RNA-seq profiling figured out HCV-related cirrhosis pathogenesis and diagnostic biomarkers.•LTB, ISLR, ZAP70, MOXD1, KLRB1, and Slitrk3, were identified as potential biomarkers.•Inflammation-enhancing pathways, cytokine-cytokine receptor interaction, NF-κB signaling, and Rheumatoid arthriti...

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Published in:Virus research 2024-11, Vol.349, p.199457, Article 199457
Main Authors: Nasr Azadani, Hossein, Nassiri Toosi, Mohssen, Shahmahmoodi, Shohreh, Nejati, Ahmad, Rahimi, Hamzeh, Farahmand, Mohammad, Keshavarz, Abolfazl, Ghorbani Motlagh, Fatemeh, Samimi-Rad, Katayoun
Format: Article
Language:English
Subjects:
Biomarkers
Cirrhosis
Gene expression
HCV
Neuropsychiatric disorders
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Summary:•Hepatic RNA-seq profiling figured out HCV-related cirrhosis pathogenesis and diagnostic biomarkers.•LTB, ISLR, ZAP70, MOXD1, KLRB1, and Slitrk3, were identified as potential biomarkers.•Inflammation-enhancing pathways, cytokine-cytokine receptor interaction, NF-κB signaling, and Rheumatoid arthritis, were highlighted in HCV-related cirrhosis.•Neural DEGs, MOXD1 and SLITRK3, were involved in neuropsychiatric disorders of cirrhotic patients.•TNF signaling, bile secretion, FoxO signaling, and axon guidance were highlighted in relation to neurological disorders in cirrhosis patients. Chronic hepatitis C virus infection is a major cause of mortality due to liver cirrhosis globally. Despite the advances in recent therapeutic strategies, there is yet a high burden of HCV-related cirrhosis worldwide concerning low coverage of newly developed antiviral therapies, insufficient validity of the current diagnostic methods for cirrhosis, and incomplete understanding of the pathogenesis in this stage of liver disease. Hence we aimed to clarify the molecular events in HCV-related cirrhosis and identify a liver-specific gene signature to potentially improve diagnosis and prognosis of the disease. Through RNA-seq transcriptome profiling of liver samples of Iranian patients with HCV-related cirrhosis, the differentially expressed genes (DEGs) were identified and subjected to functional annotation including biological process (BP) and molecular function (MF) analysis and also KEGG pathway enrichment analysis. Furthermore, the validation of RNA-seq data was investigated for seven candidate genes using qRT-PCR. Moreover, the diagnostic and prognostic power of validated DEGs were analyzed in both forms of individual DEG and combined biomarkers through receiver operating characteristic (ROC) analysis. Finally, we explored the pair-wise correlation of these six validated DEGs in a new approach. We identified 838 significant DEGs (padj ˂0.05) enriching 375 and 15 significant terms subjected to BP and MF, respectively (false discovery rate ˂ 0.01) and 46 significant pathways (p-value ˂ 0.05). Most of these biological processes and pathways were related to inflammation, immune responses, and cellular processes participating somewhat in the pathogenesis of liver disease. Interestingly, some neurological-associated genes and pathways were involved in HCV cirrhosis-related neuropsychiatric disorders. Out of seven candidate genes, six DEGs, including inflammation-related genes ISLR, LTB
ISSN:0168-1702
1872-7492
1872-7492
DOI:10.1016/j.virusres.2024.199457