{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:39:52Z","timestamp":1782509992883,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Liver cirrhosis (LC) and hepatocellular carcinoma (HCC) resulting from chronic hepatitis B virus (HBV) infection are major health concerns. Identifying critical biomarkers and molecular targets is needed for early diagnosis, prognosis, and therapy of these diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we explored the gene expression and metabolism in the liver tissues of LC, HCC, and healthy controls, to analyse and identify potential biomarkers of disease progression. Mass spectrometry imaging was used to evaluate the spatial distribution of key metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>The results revealed significant changes in gene expression and metabolic pathways along with disease progression. The upregulated genes were associated with extracellular matrix remodeling and cancer pathways, including LAMC1-3, COL9A2, COL1A1, MYL9, MYH11, and KAT2A. The downregulated genes were linked to immune response and fatty acid metabolism. Metabolomic analysis showed major changes in lipid and choline metabolism. Consistent changes in the expression of specific genes and metabolites were correlated with clinical data. Notably, metabolites such as L-acetylcarnitine, histamine, and 4-trimethylammoniobutanoic acid demonstrated high accuracy (AUC &amp;gt; 0.85) in distinguishing between healthy, LC, and HCC groups. This study identifies key gene and metabolite changes in HBV related LC and HCC, highlighting critical pathways involved in disease progression. Biomarkers like L-acetylcarnitine and KAT2A show promise for early diagnosis and prognosis, potentially improving outcomes for hepatitis liver disease patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1461456","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T06:23:44Z","timestamp":1734071024000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptomic and metabolomic analyses reveal the spatial role of carnitine metabolism in the progression of hepatitis B virus cirrhosis to hepatocellular carcinoma"],"prefix":"10.3389","volume":"15","author":[{"given":"Pengxiang","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziye","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s43066-024-00322-x","article-title":"Exploring the prognostic significance of blood carnitine and acylcarnitines in hepatitis C virus-induced hepatocellular carcinoma","volume":"14","author":"Abbass","year":"2024","journal-title":"Egypt. Liver J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41575-021-00520-7","article-title":"Cirrhosis-associated immune dysfunction","volume":"19","author":"Albillos","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"14949","DOI":"10.18632\/aging.103554","article-title":"Analysis of plasma metabolic profile, characteristics and enzymes in the progression from chronic hepatitis B to hepatocellular carcinoma","volume":"12","author":"Cai","year":"2020","journal-title":"Aging"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s12325-022-02416-7","article-title":"Complement C3 facilitates stratification of stages of chronic hepatitis b and signifies development of acute-on-chronic liver failure in acute decompensated cirrhosis","volume":"40","author":"Chen","year":"2023","journal-title":"Adv. Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"14510","DOI":"10.1074\/jbc.M113.458737","article-title":"Lysine acetyltransferase GCN5 potentiates the growth of non-small cell lung cancer via promotion of E2F1, cyclin D1, and cyclin E1 expression","volume":"288","author":"Chen","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1007\/s12672-024-01069-y","article-title":"Role of lipid metabolism in hepatocellular carcinoma","volume":"15","author":"Cheng","year":"2024","journal-title":"Discov. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10238-013-0262-5","article-title":"The effect of the severity of liver cirrhosis on the level of lipids and lipoproteins","volume":"14","author":"Chrostek","year":"2014","journal-title":"Clin. Exp. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.3892\/mmr.2014.2036","article-title":"F-actin cytoskeleton reorganization is associated with hepatic stellate cell activation","volume":"9","author":"Cui","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"5250","DOI":"10.3390\/cancers13205250","article-title":"Metabolism-associated epigenetic and immunoepigenetic reprogramming in liver cancer","volume":"13","author":"Fan","year":"2021","journal-title":"Cancers"},{"key":"B10","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.gendis.2023.02.050","article-title":"WNT\/beta-catenin signaling in hepatocellular carcinoma: the aberrant activation, pathogenic roles, and therapeutic opportunities","volume":"11","author":"Gajos-Michniewicz","year":"2024","journal-title":"Genes Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"63890","DOI":"10.18632\/oncotarget.19173","article-title":"Metabolomics and eicosanoid analysis identified serum biomarkers for distinguishing hepatocellular carcinoma from hepatitis B virus-related cirrhosis","volume":"8","author":"Gong","year":"2017","journal-title":"Oncotarget"},{"key":"B12","doi-asserted-by":"publisher","first-page":"649197","DOI":"10.3389\/fimmu.2021.649197","article-title":"High L-carnitine levels impede viral control in chronic hepatitis B virus infection","volume":"12","author":"Gu","year":"2021","journal-title":"Front. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.aca.2018.02.030","article-title":"MassImager: a software for interactive and in-depth analysis of mass spectrometry imaging data","volume":"1015","author":"He","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"B14","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1186\/s12935-022-02775-9","article-title":"Spatial metabolomics on liver cirrhosis to hepatocellular carcinoma progression","volume":"22","author":"He","year":"2022","journal-title":"Cancer Cell Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.3390\/cells8121503","article-title":"The many roles of cell adhesion molecules in hepatic fibrosis","volume":"8","author":"Hintermann","year":"2019","journal-title":"Cells"},{"key":"B16","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1136\/gut.40.4.544","article-title":"Acquired C3 deficiency in patients with alcoholic cirrhosis predisposes to infection and increased mortality","volume":"40","author":"Homann","year":"1997","journal-title":"Gut"},{"key":"B17","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"B18","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1038\/s41575-023-00760-9","article-title":"Global burden of hepatitis B virus: current status, missed opportunities and a call for action","volume":"20","author":"Hsu","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"922","DOI":"10.2174\/1386207326666230717094936","article-title":"Transcriptomic and metabolomic analysis of liver cirrhosis","volume":"27","author":"Kuang","year":"2024","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e0291798","DOI":"10.1371\/journal.pone.0291798","article-title":"Comprehensive metabolomics and transcriptomics analysis reveals protein and amino acid metabolic characteristics in liver tissue under chronic hypoxia","volume":"18","author":"Liang","year":"2023","journal-title":"PLoS ONE"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.3390\/genes13101817","article-title":"KAT2A\/E2F1 promotes cell proliferation and migration via upregulationg the exression of UBE2C in pan-cancer","volume":"13","author":"Lin","year":"2022","journal-title":"Genes"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13578-016-0114-6","article-title":"Histone acetyl transferase GCN5 promotes human hepatocellular carcinoma progression by enhancing AIB1 expression","volume":"6","author":"Majaz","year":"2016","journal-title":"Cell Biosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0130346","DOI":"10.1371\/journal.pone.0130346","article-title":"Circulating lipids are associated with alcoholic liver cirrhosis and represent potential biomarkers for risk assessment","volume":"10","author":"Meikle","year":"2015","journal-title":"PLoS ONE"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e0274544","DOI":"10.1371\/journal.pone.0274544","article-title":"Mortality burden due to liver cirrhosis and hepatocellular carcinoma in Ghana; prevalence of risk factors and predictors of poor in-hospital survival","volume":"17","author":"Nartey","year":"2022","journal-title":"PLoS ONE"},{"key":"B26","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nri3623","article-title":"Liver fibrosis and repair: immune regulation of wound healing in a solid organ","volume":"14","author":"Pellicoro","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.bpg.2011.02.009","article-title":"Liver cirrhosis","volume":"25","author":"Pinzani","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1097\/HC9.0000000000000187","article-title":"Dysregulation of lipid metabolism in the pseudolobule promotes region-specific autophagy in hepatitis B liver cirrhosis","volume":"7","author":"Pu","year":"2023","journal-title":"Hepatol. Commun."},{"key":"B29","doi-asserted-by":"publisher","first-page":"795388","DOI":"10.3389\/fmicb.2021.795388","article-title":"KAT2A promotes hepatitis B virus transcription and replication through epigenetic regulation of cccDNA minichromosome","volume":"12","author":"Qin","year":"2022","journal-title":"Front. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2904","DOI":"10.1111\/liv.16056","article-title":"High histamine levels are associated with acute-on-chronic liver failure and liver-related death in patients with advanced chronic liver disease","volume":"44","author":"Schwarz","year":"2024","journal-title":"Liver Int."},{"key":"B31","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1002\/hep.30508","article-title":"The role of complement in liver injury, regeneration, and transplantation","volume":"70","author":"Thorgersen","year":"2019","journal-title":"Hepatology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1159\/000367735","article-title":"Tumor markers for hepatocellular carcinoma: simple and significant predictors of outcome in patients with HCC","volume":"4","author":"Toyoda","year":"2015","journal-title":"Liver Cancer"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e23867","DOI":"10.1016\/j.heliyon.2023.e23867","article-title":"The role of serum acylcarnitine profiling for the detection of multiple solid tumors in humans","volume":"10","author":"Wu","year":"2024","journal-title":"Heliyon"},{"key":"B34","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1186\/s12889-024-17948-6","article-title":"Global burden of liver cirrhosis and other chronic liver diseases caused by specific etiologies from 1990 to 2019","volume":"24","author":"Wu","year":"2024","journal-title":"BMC Public Health"},{"key":"B35","doi-asserted-by":"publisher","first-page":"7840606","DOI":"10.1155\/2022\/7840606","article-title":"Circulating metabolic markers related to the diagnosis of hepatocellular carcinoma","volume":"2022","author":"Xie","year":"2022","journal-title":"J. Oncol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1080484","DOI":"10.3389\/fmicb.2022.1080484","article-title":"Human liver tissue transcriptomics revealed immunometabolic disturbances and related biomarkers in hepatitis B virus-related acute-on-chronic liver failure","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3727\/105221615X14399878166230","article-title":"The histone acetyltransferase GCN5 expression is elevated and regulated by c-Myc and E2F1 transcription factors in human colon cancer","volume":"16","author":"Yin","year":"2015","journal-title":"Gene Expr."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4821","DOI":"10.1038\/s41388-018-0298-9","article-title":"C5a induces A549 cell proliferation of non-small cell lung cancer via GDF15 gene activation mediated by GCN5-dependent KLF5 acetylation","volume":"37","author":"Zhao","year":"2018","journal-title":"Oncogene"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1461456\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T11:54:21Z","timestamp":1736855661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1461456\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,13]]},"references-count":38,"alternative-id":["10.3389\/fmicb.2024.1461456"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1461456","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,13]]},"article-number":"1461456"}}