Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis

作者：Qiumei Lin, Zeli Tang, Yuling Qin, Xueling Deng, Caibiao Wei, Fengfei Liu, Xiaolan Pan, Dengyu Liu, Tingzheng Zhan, Min Fang · 发表于：PLoS neglected tropical diseases · 年份：2024 · DOI：10.1371/journal.pntd.0011906 · 被引用次数：19 · 研究领域：Parasites and Host Interactions、Cholangiocarcinoma and Gallbladder Cancer Studies、Gallbladder and Bile Duct Disorders

BACKGROUND: Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness. METHODS: A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens. RESULTS: Compared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem...