Tumor necrosis factor alpha-induced protein 3: A key biomarker for response to ursodeoxycholic acid in primary biliary cholangitis.

Abstract

Background: The pathogenesis of primary biliary cholangitis (PBC) remains unclear. Ursodeoxycholic acid (UDCA) is the only first-line clinical treatment, but approximately 40% of patients exhibit a poor response.

Aim: To identify novel biomarkers for PBC to predict the efficacy of UDCA and enhance treatment.

Methods: Microarray expression profiling datasets were downloaded from the Gene Expression Omnibus and analyzed to identify differentially expressed genes between PBC patients and healthy controls. Immunohistochemistry was performed to validate key genes in liver tissues of the participants. Logistic regression was employed to evaluate prognostic risk factors, receiver operating characteristic curves were used to assess predictive performance, and correlations between key genes and clinicopathological characteristics were analyzed.

Results: By bioinformatic analysis, 13 genes primarily associated with the progression of PBC were identified, and tumor necrosis factor alpha-induced protein 3 (TNFAIP3) was selected for further investigation. Then expression of TNFAIP3 in PBC patients was significantly elevated compared to healthy controls on immunohistochemistry (P < 0.0001). Multivariate Cox regression analysis indicated that both TNFAIP3 and fatigue were independent risk factors for response to UDCA in PBC patients (P < 0.05). The area under the curve for TNFAIP3 and fatigue were 0.691 and 0.704, respectively, while their combination showed a significantly higher area under the curve of 0.848. The expression of TNFAIP3 was also correlated with age, albumin, total bilirubin, alkaline phosphatase and splenomegaly (P < 0.05).

Conclusion: TNFAIP3 and fatigue are independent risk factors for response to UDCA in Chinese patients with PBC. TNFAIP3 may be a potential biomarker or therapeutic target for PBC. These findings offer new insights into the pathogenesis of PBC.