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Early diagnosis is crucial for improving the therapeutic options and reducing the disease\u2010related mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate serum N\u2010glycomics as diagnostic markers for HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a comprehensive search in PubMed, EMBASE, Web of Science and Scopus through August 17, 2023. Eligible studies assessed the potential use of serum N\u2010glycomics as diagnostic biomarkers for HCC. Study selection, data extraction and quality assessment were performed by two independent reviewers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 48 articles included, 11 evaluated the utility of N\u2010glycomics for the diagnosis of HCC in whole serum while the remaining articles focused on specific protein glycoforms or protein levels. Of these specific proteins, haptoglobin, alpha\u2010fetoprotein (AFP), kininogen (Kin), \u03b1\u20101\u2010antitrypsin and Golgi protein 73 (GP73) were the most frequently studied. Increased levels of fucosylation and branching presented as the most prevalent post\u2010translational modifications of glycoproteins in patients with HCC compared to controls. Notably, glycomics\u2010based biomarkers may provide a clinical benefit for the diagnosis of early HCC, as several algorithms achieved AUCs between 0.92\u20130.97. However, these were based on single studies with limited sample sizes and should therefore be validated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alterations in serum N\u2010glycomics, characterised by increased levels of fucosylation and branching, have potential as diagnostic biomarkers for HCC. Optimisation of study design, patient selection and analysing techniques are needed before clinical implementation will be possible.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17748","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T13:15:40Z","timestamp":1698239740000},"page":"23-38","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systematic review: Glycomics as diagnostic markers for hepatocellular carcinoma"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2728-8898","authenticated-orcid":false,"given":"Emma","family":"Butaye","sequence":"first","affiliation":[{"name":"Hepatology Research Unit, Department of Internal Medicine and Pediatrics Ghent University  Ghent Belgium"},{"name":"Liver Research Center Ghent Ghent University, Ghent University Hospital  Ghent 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