CXCL8, CXCL9, CXCL10, and CXCL11 as biomarkers of liver injury caused by chronic hepatitis B

Xin Yu; Ying Chen; Lele Cui; Kaming Yang; Xumeng Wang; Linyuan Lei; Yanping Zhang; Xinyi Kong; Wanwen Lao; Zhenlin Li; Yang Liu; Yuetong Li; Changlong Bi; Chao Wu; Aixia Zhai

doi:10.3389/fmicb.2022.1052917

CXCL8, CXCL9, CXCL10, and CXCL11 as biomarkers of liver injury caused by chronic hepatitis B

Front Microbiol. 2022 Nov 24:13:1052917. doi: 10.3389/fmicb.2022.1052917. eCollection 2022.

Authors

Xin Yu¹, Ying Chen¹, Lele Cui², Kaming Yang³, Xumeng Wang^{1

4}, Linyuan Lei¹, Yanping Zhang¹, Xinyi Kong¹, Wanwen Lao³, Zhenlin Li³, Yang Liu¹, Yuetong Li³, Changlong Bi³, Chao Wu¹, Aixia Zhai¹

Affiliations

¹ Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
² Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
³ Department of Endocrinology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
⁴ Department of Microbiology, Harbin Medical University, Harbin, China.

Abstract

Background: Chronic hepatitis B (CHB) remains a significant global health problem, leading to recurrent inflammation and liver-damaging diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, although diagnostic markers for CHB are well established, the indicators for predicting liver injury caused by hepatitis B virus (HBV) infection still need to be further explored. Thus, the identification of credible infectious indicators is urgently needed to facilitate timely clinical intervention and avoid the progression of disease malignancy.

Methods: The Gene Expression Omnibus (GEO) database GSE83148 data set was used to explore the hub genes for HBV infection. The quantitative real-time polymerase chain reaction (qPCR) was used to identify the impact of HBV infection on the expression of hub gene at the cell level. At the same time, serum samples and clinical information were collected from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell experiments and Pearson correlation analysis was used to clarify hub genes correlation with HBV infection indicators and liver injury-related indicators. Finally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the differences in the expression of hub gene in liver injury diseases.

Results: Chemokine (C-X-C motif) ligand (CXCL)8, CXCL9, CXCL10, and CXCL11 were identified as hub genes in HBV infection. After HBV infection, the expression of the four chemokines was significantly increased and the concentrations secreted into serum were also increased. Moreover, the four chemokines were significantly correlated with HBV infection-related indicators and liver injury-related indicators, which were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B e antigen (HBeAg), and negatively correlated with AST/ALT ratio and hepatitis B core antibody (HBcAb). In addition, the expression of CXCL9, CXCL10, and CXCL11 in HCC tissues was significantly higher than in normal tissues.

Conclusion: Using a combination of bioinformatics, cell experiments, and clinical correlation analysis, this study showed that CXCL8, CXCL9, CXCL10, and CXCL11 can be used as serum biomarkers to forecast liver injury caused by HBV infection.

Keywords: CXCL10; CXCL11; CXCL8; CXCL9; hepatitis B virus.