Resumen de Identification and validation of plasma AGRN as a novel diagnostic biomarker of hepatitis B Virus-related chronic hepatitis and liver fibrosis/cirrhosis
Rong Ai, Lu Li, Xiwei Yuan, Dandan Zhao, Tongguo Miao, Shiming Dong, Chen Dong, Yao Dou, Mengmeng Hou, Yuemin Nan
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.
