Clonorchis sinensis-infected hepatocellular carcinoma exhibits distinct tumor microenvironment and molecular features

作者：Junxian Chen, Caibiao Wei, Wen‐Cheng Huang, Taijun Huang, Lingling Zhou, Yulong Xu, Yuling Qin, Qiumei Lin, Fengfei Liu, Xiaolan Pan, Zeli Tang, Weilong Yang, Min Fang · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1526699 · 被引用次数：3 · 研究领域：Parasites and Host Interactions、Neurological diseases and metabolism、Oral and gingival health research

Objectives Clonorchis sinensis ( Cs )-infected hepatocellular carcinoma (HCC) patients have a poorer prognosis than non- Cs -infected HCCs. However, the molecular mechanisms of Cs -infected HCC remain unclear. To address this, this study aims to uncover the tumor microenvironment and molecular features that may contribute to these poor outcomes. Methods The research involved bulk RNA sequencing of paired tumor and adjacent tissue samples from 10 Cs + HCC and 10 Cs - HCC patients. Differentially expressed genes were identified, followed by enrichment analyses to reveal functional changes. Survival analysis of the top 10 up- and down-regulated genes in Cs + HCC tumors was performed using TCGA database. Additionally, clinical data from 1,461 HCC patients were retrospectively analyzed to assess the impact of Cs infection on microvascular invasion and metastasis rates. In vitro assays were also conducted using Cs excretory/secretory products ( Cs ESPs) to examine their effect on HCC cells and HUVECs. Results We identified 785 up-regulated and 675 down-regulated genes in Cs + HCC tumors compared to Cs - HCC tumors, enriched in pathways related to extracellular matrix remodeling and immunosuppression. Survival analysis revealed that the top 10 up-regulated genes are associated with HCC poor prognosis. Clinical data from 1,461 HCC patients showed Cs infection increased microvascular invasion and metastasis rates. In vitro , Cs ESPs products enhanced migration and invasion in HCC cell...