Clonorchis sinensis infection contributes to hepatocellular carcinoma progression via enhancing angiogenesis

Abstract

Background Clonorchis sinensis (C. sinensis) infection plays an important role in the progression of hepatocarcinogenesis. However, its specific role in HCC progression remains unclear. This study aimed to investigate whether C. sinensis contributes to angiogenesis in HCC. Methods A comprehensive clinical analysis was conducted on 947 HCC patients, divided into two groups: C. sinensis (-) HCC and C. sinensis (+) HCC. Kaplan–Meier survival curves and log-rank tests were utilized to assess survival outcomes. Microvessel density (MVD) was evaluated through CD34 immunohistochemistry on hepatectomy specimens. A chemistry analyzer and blood analyzer were employed to measure the concentration of circulating angiogenesis-related biomarkers. Quantitative reverse transcription-PCR (qRT-PCR) was used to analyze the expression of angiogenesis-related genes (CD34, Ang1, Ang2, VEGF, PDGF) in HCC tissues. Results C. sinensis infection was associated with poorer outcomes in HCC patients, with significantly shorter overall survival (OS) (p = 0.014) and recurrence-free survival (RFS) (p<0.001). Notably, C. sinensis infection led to an upregulation of MVD in HCC tissues (p = 0.041). C. sinensis (+) HCC patients exhibited significantly higher levels of circulating angiogenesis-related biomarkers, including MONO (p = 0.004), EOSO (p < 0.001), C3 (p = 0.001), FIB (p = 0.010), PLT (p = 0.003), LDH (p = 0.004), GLDH (p = 0.003), compared to C. sinensis (-) HCC patients. Moreover, qRT-PCR analysis revealed that most angiogenesis-related genes were overexpressed in patients with C. sinensis infection. Conclusion C. sinensis infection is closely associated with inflammatory responses and may promote metabolic reprogramming in HCC, thereby enhancing its malignant characteristics.