Correlation of local and serum CircHIPK3 expressions with the progression of liver fibrosis/cirrhosis

Background and study aims: This study was aimed to validate the correlation of circular RNA HIPK3 (CircHIPK3) expression in serum and tissues with the progression of liver fibrosis (LF) and liver cirrhosis (LC).

Patients and methods: Serum CircHIPK3 expressions were detected in 120 patients with LF/LC and 120 healthy controls (HCs). CircHIPK3 expression in tissues was detected in 120 fibrotic liver tissues and compared to 57 healthy liver tissues from patients with hepatic hemangioma. The expressions of CircHIPK3, TGF-β1, and CollA1 mRNAs were assessed by qRT-PCR. The Child-Pugh (CP) classification was used to evaluate disease severity. The Ishak score was applied to assess LF/LC in liver biopsy samples. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also investigated. Receiver operating characteristic (ROC) analysis was conducted to assess the diagnostic value of CircHIPK3 expressions in serum and tissues.

Results: CircHIPK3 expressions in serum and tissues were upregulated in patients with LF/LC compared to HCs. The patient group comprised 39 with CP class A (CP-A), 45 with CP class B (CP-B), and 36 with CP class B (CP-C). Patients with CP-C had markedly increased serum and local CircHIPK3 levels compared to those with CP-B and CP-A. Patients with CP-B showed upregulated CircHIPK3 expressions in serum and tissues compared to CP-A with statistical significance. ROC curve analysis indicated that CircHIPK3 expressions in both serum and tissues may serve as potential diagnostic indicators for the progression of LF/LC. Moreover, serum CircHIPK3 expressions were positively associated with serum ALT and AST levels. Tissue CircHIPK3 expressions were positively correlated with tissue TGF-β1 and CollA1 mRNA expressions. In addition, both serum and tissue CircHIPK3 expressions were positively associated with the Ishak score.

Conclusions: For the first time, this study demonstrated the positive correlation of CircHIPK3 expressions in both serum and tissues with the progression of LF/LC, regardless of etiology. CircHIPK3 might play a significant role in the development of LF/LC and act as a potential therapeutic target for these conditions.