Evaluation of the expression of fibrosis-related genes as non-invasive diagnostic biomarkers for cirrhotic HCV-infected patients

•Liver cirrhosis triggers architectural disruption and chronic inflammation.•Early detection of cirrhosis is mandatory to minimize the mortality risk.•TGFβ signaling pathway is a pillar regulator in liver cirrhosis.•TGFβ1and TGFβ2 genes are correlated with advanced cirrhosis.•TGFβ2 proteomic level i...

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Published in:Cytokine (Philadelphia, Pa.) Pa.), 2024-10, Vol.182, p.156714, Article 156714
Main Authors: El-Meguid, Mai Abd, Lotaif, Lotaif Mostafa, Salum, Ghada M., Fotouh, Basma E., Salama, Rabab Maamoun, Salem, Mohamed Ibrahim Seif Elnasr, El Awady, Mostafa K., Abdel Aziz, Ashraf Omar, Dawood, Reham M.
Format: Article
Language:English
Subjects:
Cirrhosis
Cytokines
Gene expression
HCV
PBMCs
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Summary:•Liver cirrhosis triggers architectural disruption and chronic inflammation.•Early detection of cirrhosis is mandatory to minimize the mortality risk.•TGFβ signaling pathway is a pillar regulator in liver cirrhosis.•TGFβ1and TGFβ2 genes are correlated with advanced cirrhosis.•TGFβ2 proteomic level is linked to cirrhosis progression. Liver cirrhosis is a condition with high mortality that poses a significant health and economic burden worldwide. The clinical characteristics of liver cirrhosis are complex and varied. Therefore, the evaluation of immune infiltration-involved genes incirrhosis has become mandatory in liver disease research, not only to identify the potential biomarkers but also to provide important insights into the underlying mechanisms of the disease. In this study, we aimed to investigate the expression profile of cytokine genes in peripheral blood mononuclear cells (PBMCs) of HCV patients and identify the gene expression signature associated with advanced cirrhosis. A cross-sectional study of 90 HCV genotype 4 patients, including no fibrosis patients (F0, n = 24), fibrotic patients (F1-F3, n = 36), and cirrhotic patients (F4, n = 30) has been conducted. The expression of cytokine genes was analyzed by quantitative real-time PCR in the subjects’ PBMCs, and the serum level of TGFβ2 was measured by ELISA. Our findings showed that the expression level of the TGIF1 transcript was lower in cirrhotic and fibrotic patients compared to no fibrosis patients (p = 0.046 and 0.022, respectively). Also, there was an upregulation of the TGFβ1 gene in cirrhotic patients relative to fibrotic patients (p = 0.015). Additionally, the cirrhotic patients had higher expression levels of the TGF-β2 transcript and elevated levels of the TGF-β2 protein than patients with no cirrhosis or fibrosis. According to the ROC analysis, TGFβ1, TGIF1 transcripts, and TGFβ2 protein have a good discriminatory performance in distinguishing between cirrhotic, fibrotic, and non-fibrotic patients. Our results suggested that the expression of TGIF1, TGF-β1, and TGF-β2 genes in PBMCs may provide a valuable tool for identifying patients with advanced cirrhosis and that TGF-β and TGIF1 may be potential biomarkers for cirrhosis. These findings may have implications for the diagnosis and treatment of cirrhosis in HCV patients.
ISSN:1043-4666
1096-0023
1096-0023
DOI:10.1016/j.cyto.2024.156714