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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Parasite Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1489077

Serum proteomic and metabolomic profiling of hepatocellular carcinoma patients co-infected with Clonorchis sinensis

Provisionally accepted
Zeli Tang Zeli Tang 1Caibiao Wei Caibiao Wei 2Xueling Deng Xueling Deng 1Qiumei Lin Qiumei Lin 2Qiping Hu Qiping Hu 1Shitao Li Shitao Li 1Jilong Wang Jilong Wang 1Yuhong Wu Yuhong Wu 1Dengyu Liu Dengyu Liu 1Min Fang Min Fang 2Tingzheng Zhan Tingzheng Zhan 1*
  • 1 Guangxi Medical University, Nanning, Guangxi Zhuang Region, China
  • 2 Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Region, China

The final, formatted version of the article will be published soon.

    Background: Clonorchis sinensis (C. sinensis) infection is a significant risk factor for hepatocellular carcinoma (HCC), yet its underlying mechanisms remain poorly understood.This study aimed to investigate the impact of C. sinensis infection on the serum proteomic and metabolomic profiling of HCC patients, focusing on the potential mechanisms. Method: A retrospective clinical analysis was conducted on 1121 HCC patients, comparing those with and without C. sinensis infection. The influence of C. sinensis on serum proteome and metabolome in HCC was further assessed. Result: C. sinensis infection correlated with a younger age at cancer onset, male predominance, advanced cancer stage, liver cirrhosis, and microvascular invasion in HCC patients. It also associated with shorter overall survival (OS) and recurrence-free survival (RFS). The levels of blood lipids (e.g., APO-A, HDL-C, and TG) were significantly altered after C. sinensis infection. Proteomic and metabolomic analyses revealed metabolic reprogramming caused by C. sinensis, with excessive depletion of argininosuccinate synthase (ASS) and D-glucose as potential factors in C. sinensis-associated HCC malignancy. Key molecules ILF2, CNN2, OLFM4, NOTCH3, and LysoPA were implicated in HCC progression. Furthermore, C. sinensis triggered inflammation, insulin resistance, and pro-tumor immune escape, and exacerbated the complication of degenerative diseases. Conclusion: This study not only provides compelling evidence for elucidating the mechanisms underlying C. sinensis-mediated HCC development but also identifies potential therapeutic targets for HCC patients co-infected with C. sinensis.

    Keywords: Clonorchis sinensis, Hepatocellular Carcinoma, prognosis, proteomic, metabolomic

    Received: 31 Aug 2024; Accepted: 10 Dec 2024.

    Copyright: © 2024 Tang, Wei, Deng, Lin, Hu, Li, Wang, Wu, Liu, Fang and Zhan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Tingzheng Zhan, Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Region, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.