Publication: Identification and validation of plasma AGRN as a novel diagnostic biomarker of hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosisy
Authors
Ai, Rong ; Li, Lu ; Yuan, Xiwei ; Zhao, Dandan ; Miao, Tongguo ; Guan, Weiwei ; Dong, Shiming ; Dong, Chen ; Dou, Yao ; Hou, Mengmeng ; Nan, Yuemin
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Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
https://doi.org/10.14670/HH-18-695
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info:eu-repo/semantics/article
Description
Abstract
Objective. The aim of this study was to find
novel biomarkers and develop a non-invasive, effective
diagnostic model for hepatitis B Virus-related chronic
hepatitis and liver fibrosis/cirrhosis.
Method. Quantitative real-time polymerase chain
reaction (qRT-PCR) was utilized to assess the expression
of differentially expressed genes (AGRN, JAG1, CCL5,
ID3, CCND1, and CAPN2) in peripheral blood
mononuclear cells (PBMCs) from healthy subjects,
chronic hepatitis B (CHB), and liver fibrosis/cirrhosis
(LF/LC) patients. The molecular mechanisms underlying
AGRN-regulated CHB were further explored and
verified in LX2 cells, in which small interfering RNA
(siRNA) was used to block AGRN gene expression.
Finally, enzyme-linked Immunosorbent Assay (ELISA)
was used to measure AGRN protein expression in 100
healthy volunteers, 100 CHB patients, and 100 LF/LC
patients, and the efficacy of the diagnostic model was
assessed by the Area Under the Curve (AUC).
Results. AGRN mRNA displayed a steady rise in the
PBMCs of normal, CHB, and LF/LC patients. Besides,
AGRN expression was markedly elevated in activated
LX2 cells, whereas the expression of COL1 and α-SMA
decreased when AGRN was inhibited using siRNA. In
addition, downregulation of AGRN can reduce the gene
expression of β-catenin and c-MYC while upregulating
the expression of GSK-3β. Furthermore, PLT and AGRN
were used to develop a non-invasive diagnostic model
(PA). To identify CHB patients from healthy subjects,
the AUC of the PA model was 0.951, with a sensitivity
of 87.0% and a specificity of 91.0%. The AUC of the PA
model was 0.922 with a sensitivity of 82.0% and a
specificity of 90.0% when differentiating between
LF/LC and CHB patients.
Conclusion. The current study indicated that AGRN
could be a potential plasma biomarker and the
established PA model could improve the diagnostic
accuracy for HBV-related liver diseases.
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Citation
Histology and Histopathology, Vol.39, nº8, (2024)
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