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This review synthesizes current knowledge of liver cancer trends, etiology, and literature-based correlates for hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma. Reported metabolic disturbances include TCA dysfunction (especially in HB and HCC), while CCA shows point mutations and altered signaling. All cases warrant further study of upstream and downstream events, with shared pathway dysregulation involving WNT/β-catenin and P13K/AKT/mTOR and changes in FGFR.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/primary-liver-cancers-connecting-the-dots-of-cellular-studies-and-epidemiology-with-metabolomics/376553/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/primary-liver-cancers-connecting-the-dots-of-cellular-studies-and-epidemiology-with-metabolomics/376553.png","ImageObject",300,407,{"name":92,"@type":93},"MrHarris58","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What gap does the review propose metabolomics can help address in liver cancer research?","Question",{"text":113,"@type":114},"It highlights a gap between molecular studies and epidemiological studies and suggests that metabolomics may bridge this divide by connecting systemic metabolic patterns with cellular mechanisms.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which liver cancer types does the review focus on?",{"text":118,"@type":114},"The review centers on hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatoblastoma (HB), including their reported etiology and related correlates.",{"name":120,"@type":111,"acceptedAnswer":121},"What common pathways and metabolic dysfunctions are reported across liver cancer cases?",{"text":122,"@type":114},"The review reports dysfunction in the WNT/β-catenin and P13K/AKT/mTOR pathways, changes in FGFR, and dysfunction in tricarboxylic acid (TCA) metabolism for key subtypes, along with other metabolite alterations.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},376553,1790366891,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":31},687212988360,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Review  \nPrimary Liver Cancers: Connecting the Dots of Cellular Studies and Epidemiology with Metabolomics  \nShoma Berkemeyer  \nCitation: Berkemeyer, S. Primary  \nLiver Cancers: Connecting the Dots of Cellular Studies and Epidemiology with Metabolomics. Int. J. Mol. Sci. 2023, 24, 2409. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms24032409](10.3390/ijms24032409)  \nAcademic Editor: Jing-Hsiung James Ou  \nReceived: 30 December 2022  \nRevised: 21 January 2023  \nAccepted: 24 January 2023  \nPublished: 26 January 2023  \nCopyright: © 2023 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nFaculty of Agricultural Sciences and Landscape Architecture, Osnabrueck University of Applied Sciences, Am Kruempel 31, 49090 Osnabrueck, Germany; [s.berkemeyer@hs-osnabrueck.de](s.berkemeyer@hs-osnabrueck.de)  \nAbstract: Liver cancers are rising worldwide. Between molecular and epidemiological studies, a research gap has emerged which might be amenable to the technique of metabolomics. This review investigates the current understanding of liver cancer's trends, etiology and its correlates with existing literature for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA) and hepatoblastoma (HB) . Among additional factors, the literature reports dysfunction in the tricarboxylic acid metabolism, primarily for HB and HCC, and point mutations and signaling for CCA. All cases require further investigation of upstream and downstream events. All liver cancers reported dysfunction in the WNT/􀀌-catenin and P13K/AKT/mTOR pathways as well as changes in FGFR. Metabolites of IHD1, IDH2, miRNA, purine, Q10, lipids, phosphatidylcholine, phosphatidylethanolamine, acylcarnitine, 2-HG and propionyl-CoA emerged as crucial and there was an attempt to elucidate the WNT/􀀌-cateninand P13K/AKT/mTOR pathways metabolomically.  \nKeywords: hepatocellular carcinoma; cholangiocarcinoma; hepatoblastoma; metabolomics; WNT/􀀌 -catenin pathway; P13K/AKT/mTOR pathway; lipid; TCA  \n1. Introduction  \nLiver cancer is the third largest cause of cancer deaths worldwide [1] . Globally, it is the sixth most common cancer [2] . The global incidence is increasing [2] . The primary liver cancer in adults is hepatocellular carcinoma (HCC), which accounts for about 80– 90% of cases [2] . The second most common liver cancer is Cholagniocarinoma (CCA), which accounts for 10–15% of the cases [2] . Remnant cases of liver cancer are hepatocellular cholangiocarcinoma, angiosarcoma and hepatoblastoma (HB) [2] . The primary liver cancersin children are HB and HCC [2,3] . HB accounts for about 70% of the cases and HCC accounts for about 27% of the cases [2,3] . Each type and sub-type of liver cancer has its own etiology. Genetic investigation of liver cancers attributes damage and mutations to specific genes in cancer etiology. An example is mutation A235G in the catenin beta 1 (CTNNB1) gene (refer to Abbreviations), which led to upregulation of the gene in HB and HCC [3,4] . Another example is upregulation of C-X3-C motif chemokine (CX3CL1) gene, due to repeated missense mutation on exon 3 [3] . This leads to substitution of the amino acid alanine by glycine in protein translation, with changes in inflammation and immunity metabolites [3] . These connections between genes and systemic metabolites are tedious and require investigation. Between large-scale population and epidemiological studies [1,2] and cellular studies [3,4] metabolomics offer a means of investigation, which incorporates systemic adjustments of maintenance of homeostasis, systemic and cellular feedback loopsand compensatory mechanisms. Metabolomics is increasingly offering a means to connect basic science with clinical epidemio","cbCaiteIfl63CrlN","https://ap.wps.com/l/cbCaiteIfl63CrlN","pdf",1428437,"English","# Introduction\n# Current Understanding of Liver Cancer Trends, Etiology and Correlates\n## Current Epidemiological and Molecular Understanding of Hepatoblastoma (HB)","[{\"question\":\"What gap does the review propose metabolomics can help address in liver cancer research?\",\"answer\":\"It highlights a gap between molecular studies and epidemiological studies and suggests that metabolomics may bridge this divide by connecting systemic metabolic patterns with cellular mechanisms.\"},{\"question\":\"Which liver cancer types does the review focus on?\",\"answer\":\"The review centers on hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatoblastoma (HB), including their reported etiology and related correlates.\"},{\"question\":\"What common pathways and metabolic dysfunctions are reported across liver cancer cases?\",\"answer\":\"The review reports dysfunction in the WNT/β-catenin and P13K/AKT/mTOR pathways, changes in FGFR, and dysfunction in tricarboxylic acid (TCA) metabolism for key subtypes, along with other metabolite alterations.\"}]","Primary Liver Cancers - Connecting the Dots of Cellular Studies and Epidemiology with Metabolomics | PDF",1790219940]