Qiumei Lin, Junxian Chen, Lingling Zhou, Min Fang, Caibiao Wei, Taijun Huang, Yulong Xu, Jie Gao, Fengfei Liu, Zeli Tang, Jian-Kang Zhu, Weilong Yang
{"title":"华支睾吸虫相关肝癌中乳酸代谢基因调控的多组学分析。","authors":"Qiumei Lin, Junxian Chen, Lingling Zhou, Min Fang, Caibiao Wei, Taijun Huang, Yulong Xu, Jie Gao, Fengfei Liu, Zeli Tang, Jian-Kang Zhu, Weilong Yang","doi":"10.1186/s13071-025-06947-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Although recent research has highlighted lactylation, a post-translational modification driven by elevated lactate levels, as a critical regulator of key cellular pathways in hepatocellular carcinoma (HCC), its contribution to the poor prognosis of Clonorchis sinensis (Cs)-infected HCC remains poorly understood.</p><p><strong>Methods: </strong>We first identified the significant upregulation of the lactate metabolism enzyme LDH in Cs-infected HCC patients through clinical retrospective analysis. We then conducted a multi-omics analysis (RNA-Seq, ATAC-Seq, WGBS-Seq, oxWGBS-Seq, and ChIP-Seq) to examine the differences in 392 lactate metabolism-related genes (LMRGs) between Cs-infected and Cs-noninfected HCC tumors. Six key differentially expressed LMRGs were further validated using RT-qPCR assays to confirm their expression and potential role in HCC progression.</p><p><strong>Results: </strong>The differential expression levels of 8 LMRGs, along with 71 accessible regions and 42 CpG sites in the promoters of LMRGs, were identified. Notably, we also demonstrated that histone modifications, including H3K9ac, H3K79me2, H3K4me2, H3K4me3, H3K27ac, and H3K4me1, were associated with chromatin accessibility in the promoters of LMRGs. Finally, the TCGA-LIHC cohort confirmed that the differential expression of LMRGs between Cs-infected and Cs-noninfected HCC tumors significantly affects the survival outcomes of HCC.</p><p><strong>Conclusions: </strong>Our findings revealed that lactylation plays an important role in reshaping the characteristics of HCC during Cs infection, expanding our understanding of the unique features of Cs-infected HCC.</p>","PeriodicalId":19793,"journal":{"name":"Parasites & Vectors","volume":"18 1","pages":"301"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302829/pdf/","citationCount":"0","resultStr":"{\"title\":\"Multi-omics analysis of lactate metabolism gene regulation in Clonorchis sinensis-associated hepatocellular carcinoma.\",\"authors\":\"Qiumei Lin, Junxian Chen, Lingling Zhou, Min Fang, Caibiao Wei, Taijun Huang, Yulong Xu, Jie Gao, Fengfei Liu, Zeli Tang, Jian-Kang Zhu, Weilong Yang\",\"doi\":\"10.1186/s13071-025-06947-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Although recent research has highlighted lactylation, a post-translational modification driven by elevated lactate levels, as a critical regulator of key cellular pathways in hepatocellular carcinoma (HCC), its contribution to the poor prognosis of Clonorchis sinensis (Cs)-infected HCC remains poorly understood.</p><p><strong>Methods: </strong>We first identified the significant upregulation of the lactate metabolism enzyme LDH in Cs-infected HCC patients through clinical retrospective analysis. We then conducted a multi-omics analysis (RNA-Seq, ATAC-Seq, WGBS-Seq, oxWGBS-Seq, and ChIP-Seq) to examine the differences in 392 lactate metabolism-related genes (LMRGs) between Cs-infected and Cs-noninfected HCC tumors. Six key differentially expressed LMRGs were further validated using RT-qPCR assays to confirm their expression and potential role in HCC progression.</p><p><strong>Results: </strong>The differential expression levels of 8 LMRGs, along with 71 accessible regions and 42 CpG sites in the promoters of LMRGs, were identified. Notably, we also demonstrated that histone modifications, including H3K9ac, H3K79me2, H3K4me2, H3K4me3, H3K27ac, and H3K4me1, were associated with chromatin accessibility in the promoters of LMRGs. Finally, the TCGA-LIHC cohort confirmed that the differential expression of LMRGs between Cs-infected and Cs-noninfected HCC tumors significantly affects the survival outcomes of HCC.</p><p><strong>Conclusions: </strong>Our findings revealed that lactylation plays an important role in reshaping the characteristics of HCC during Cs infection, expanding our understanding of the unique features of Cs-infected HCC.</p>\",\"PeriodicalId\":19793,\"journal\":{\"name\":\"Parasites & Vectors\",\"volume\":\"18 1\",\"pages\":\"301\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-07-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302829/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Parasites & Vectors\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13071-025-06947-0\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Parasites & Vectors","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13071-025-06947-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PARASITOLOGY","Score":null,"Total":0}
Multi-omics analysis of lactate metabolism gene regulation in Clonorchis sinensis-associated hepatocellular carcinoma.
Background: Although recent research has highlighted lactylation, a post-translational modification driven by elevated lactate levels, as a critical regulator of key cellular pathways in hepatocellular carcinoma (HCC), its contribution to the poor prognosis of Clonorchis sinensis (Cs)-infected HCC remains poorly understood.
Methods: We first identified the significant upregulation of the lactate metabolism enzyme LDH in Cs-infected HCC patients through clinical retrospective analysis. We then conducted a multi-omics analysis (RNA-Seq, ATAC-Seq, WGBS-Seq, oxWGBS-Seq, and ChIP-Seq) to examine the differences in 392 lactate metabolism-related genes (LMRGs) between Cs-infected and Cs-noninfected HCC tumors. Six key differentially expressed LMRGs were further validated using RT-qPCR assays to confirm their expression and potential role in HCC progression.
Results: The differential expression levels of 8 LMRGs, along with 71 accessible regions and 42 CpG sites in the promoters of LMRGs, were identified. Notably, we also demonstrated that histone modifications, including H3K9ac, H3K79me2, H3K4me2, H3K4me3, H3K27ac, and H3K4me1, were associated with chromatin accessibility in the promoters of LMRGs. Finally, the TCGA-LIHC cohort confirmed that the differential expression of LMRGs between Cs-infected and Cs-noninfected HCC tumors significantly affects the survival outcomes of HCC.
Conclusions: Our findings revealed that lactylation plays an important role in reshaping the characteristics of HCC during Cs infection, expanding our understanding of the unique features of Cs-infected HCC.
期刊介绍:
Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish.
Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.