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A Bioinformatic Analysis of Correlations between Polymeric Immunoglobulin Receptor (PIGR) and Liver Fibrosis
Yuan Zhang1, Wenjun Lu2, Xiaorong Chen1
1Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Objective:
This study is aimed at investigating the enriched functions of polymeric immunoglobulin receptor (PIGR) and its correlations with liver fibrosis stage.
Methods:
PIGR mRNA expression in normal liver, liver fibrosis, hepatic stellate cells (HSCs), and hepatitis virus infection samples was calculated in Gene Expression Omnibus (GEO) and Oncomine databases. Enrichment analysis of PIGR-related genes was conducted in Metascape and Gene Set Enrichment Analysis (GSEA). Logistic model and ROC curve were performed to evaluate the correlations between pIgR and liver fibrosis.
Results:
PIGR mRNA was upregulated in advanced liver fibrosis, cirrhosis compared to normal liver (all p < 0.05). PIGR mRNA was also overexpressed in activated HSCs compared to senescent HSCs, liver stem/progenitor cells, and reverted HSCs (all p < 0.05). Enrichment analysis revealed that PIGR-related genes involved in the defense response to virus and interferon (IFN) signaling. In GEO series, PIGR mRNA was also upregulated by hepatitis virus B, C, D, and E infection (all p < 0.05). After adjusting age and gender, multivariate logistic regression models revealed that high PIGR in the liver was a risk factor for liver fibrosis (OR = 82.2, p < 0.001). The area under curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of PIGR for liver fibrosis stage >2 were 0.84, 0.86, 0.7, 0.61, and 0.90.
Conclusion:
PIGR was correlated with liver fibrosis and might involve in hepatitis virus infection and HSC transdifferentiation.
Insights
Polymeric immunoglobulin receptor (PIGR) is upregulated in advanced liver fibrosis and correlates with hepatitis virus infection. High PIGR levels indicate a significant risk factor for liver fibrosis progression.
Area of Science:
- Hepatology
- Immunology
- Molecular Biology
Background:
- Liver fibrosis is a significant health concern with complex underlying mechanisms.
- The role of polymeric immunoglobulin receptor (PIGR) in liver fibrosis remains incompletely understood.
Purpose of the Study:
- To investigate the functional roles of PIGR.
- To determine the correlation between PIGR expression and the stage of liver fibrosis.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) and Oncomine databases for PIGR mRNA expression analysis.
- Performed enrichment analysis using Metascape and GSEA for PIGR-related genes.
- Employed logistic regression and ROC curve analysis to assess PIGR's correlation with liver fibrosis.
Main Results:
- PIGR mRNA expression was significantly elevated in advanced liver fibrosis and cirrhosis compared to normal liver tissue.
- PIGR was overexpressed in activated hepatic stellate cells (HSCs) and upregulated by hepatitis virus infections (B, C, D, E).
- High PIGR levels in the liver were identified as a strong risk factor for liver fibrosis (OR = 82.2, p < 0.001) with high diagnostic accuracy (AUC = 0.84).
Conclusions:
- PIGR expression is closely associated with liver fibrosis progression.
- PIGR may play a role in the pathogenesis of hepatitis virus infections and HSC activation/transdifferentiation.
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