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

ABSTRACT: Serum proteomic of hepatocellular carcinoma patients co-infected with Clonorchis sinensis

ORGANISM(S): Homo Sapiens

SUBMITTER: Zeli Tang

PROVIDER: PXD051871 | iProX | Mon Apr 29 00:00:00 BST 2024

REPOSITORIES: iProX

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Clonorchis sinensis (C. sinensis) infection remodels the chromatin accessibility of hepatocellular carcinoma

Project description:Background: Liver cancer is the third deadliest type of cancer, posing a serious threat to human health. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. C. sinensis, classified as a definite group I carcinogen by the IARC (International Agency for Research on Cancer), is an important risk factor for HCC. Although many studies have shown that C. sinensis infection affects the prognosis of HCC patients, the specific mechanisms are still unclear, especially the dynamics and regulatory roles of chromatin accessibility. Results: In this study, we integrated ATAC-seq, RNA-seq, and ChIP-seq data to elucidate changes in the epigenetics of HCC after the C. sinensis infection. Many different accessibility regions (DARs) were identified both in tumors and adjacent tissue after the C. sinensis infection. Meanwhile, top TFs whose motifs were enriched in DAR were found, such as HNF4a, FOXI1, etc. Although there were slight deviations, epigenetic changes were found to be consistent with gene expression levels. We also revealed that H3K9ac, H3K4me2, H3K4me3, H3K27ac, and H3K4me1 were associated with chromatin accessibility. Importantly, we also found potential evidence that C. sinensis infection would alter the spatial structure of the HCC genome. Finally, both molecular experimental results and clinical data certified that C. sinensis infection would promote the metastasis of HCC. Conclusions: C. sinensis infection will remodel the chromatin accessibility of HCC, leading to changes in gene expression levels. This study provides conclusive evidence that C. sinensis infection alters the epigenetics of HCC.

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Clonorchis sinensis infection alters the methylation and hydroxymethylation of hepatocellular carcinoma

Project description:Clonorchis sinensis (Cs) infection is prevalent in Southeast Asia and has been classified as a Group I carcinogen by the International Agency for Research on Cancer, posing significant risks to the human liver and biliary system. While recent studies have linked Cs infection to poorer outcomes in hepatocellular carcinoma (HCC) patients, the precise molecular mechanisms underlying its effect on HCC remain to be fully elucidated. This study investigates the epigenetic changes in Cs-infected HCC using whole-genome bisulfite sequencing and whole-genome oxidative bisulfite sequencing to map 5-methylcytosine and 5-hydroxymethylcytosine profiles at single-nucleotide resolution. We identified 29 differentially methylated regions and 13 differentially hydroxymethylated regions in Cs-infected HCC, which were associated with 28 differentially methylated/hydroxymethylated-associated genes (DAGs/DhAGs). The methylation levels of four promoter Cytosine-phosphate-Guanine (CpG) sites of DAGs/DhAGs were found to correlate with prognosis in Cs-infected HCC, while two key DMR/DhMR-associated genes, DHDH and KCNQ3, were significantly linked to overall survival of HCC. Our study provides the first detailed epigenetic map of Cs-associated HCC, uncovering novel insights into potential biomarkers and therapeutic targets that could enhance prognostic predictions and inform treatment strategies for patients affected by this condition.

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