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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Clonorchis sinensis<\/jats:italic>\n                      (\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      ) 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\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      infection on the serum proteomic and metabolomic profiling of HCC patients, focusing on the potential mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      A retrospective clinical analysis was conducted on 1121 HCC patients, comparing those with and without\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      infection. The influence of\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      on serum proteome and metabolome in HCC was further assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      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\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      infection. Proteomic and metabolomic analyses revealed metabolic reprogramming caused by\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      , with excessive depletion of argininosuccinate synthase (ASS) and D-glucose as potential factors in\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      -associated HCC malignancy. Key molecules ILF2, CNN2, OLFM4, NOTCH3, and LysoPA were implicated in HCC progression. Furthermore,\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      triggered inflammation, insulin resistance, and pro-tumor immune escape, and exacerbated the complication of degenerative diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study not only provides compelling evidence for elucidating the mechanisms underlying\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      -mediated HCC development but also identifies potential therapeutic targets for HCC patients co-infected with\n                      <jats:italic>C. sinensis<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  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