{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:27:01Z","timestamp":1778628421652,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260110 81870449 82170674 51933011"],"award-info":[{"award-number":["82260110 81870449 82170674 51933011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M653904XB"],"award-info":[{"award-number":["2019M653904XB"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015310","name":"Natural Science Foundation of Xinjiang","doi-asserted-by":"publisher","award":["2020D01C006"],"award-info":[{"award-number":["2020D01C006"]}],"id":[{"id":"10.13039\/501100015310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Hepatocellular carcinoma (HCC) has become the world\u2019s primary cause of cancer death. Obesity, hyperglycemia, and dyslipidemia are all illnesses that are part of the metabolic syndrome. In recent years, this risk factor has become increasingly recognized as a contributing factor to HCC. Around the world, non-alcoholic fatty liver disease (NAFLD) is on the rise, especially in western countries. In the past, the exact pathogenesis of NAFLD that progressed to metabolic risk factors (MFRs)-associated HCC has not been fully understood.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Two groups of the GEO dataset (including normal\/NAFLD and HCC with MFRs) were used to analyze differential expression. Differentially expressed genes of HCC were verified by overlapping in TCGA. In addition, functional enrichment analysis, modular analysis, Receiver Operating Characteristic (ROC) analysis, LASSO analysis, and Genes with key survival characteristics were analyzed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We identified six hub genes (FABP5, SCD, CCL20, AGPAT9(GPAT3), PLIN1, and IL1RN) that may be closely related to NAFLD and HCC with MFRs. We constructed survival and prognosis gene markers based on FABP5, CCL20, AGPAT9(GPAT3), PLIN1, and IL1RN.This gene signature has shown good diagnostic accuracy in both NAFLD and HCC and in predicting HCC overall survival rates.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> As a result of the findings of this study, there is some guiding significance for the diagnosis and treatment of liver disease associated with NAFLD progression.<\/jats:p>","DOI":"10.3389\/fgene.2023.1066410","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T06:09:40Z","timestamp":1678082980000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Key genes associated with non-alcoholic fatty liver disease and hepatocellular carcinoma with metabolic risk factors"],"prefix":"10.3389","volume":"14","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beibei","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghai","family":"Lian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiusheng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoguang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangping","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.bbadis.2017.11.026","article-title":"Emerging metabolic risk factors in hepatocellular carcinoma and their influence on the liver microenvironment","volume":"1864","author":"Agosti","year":"2018","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1007\/s00535-015-1159-8","article-title":"Expression of connective tissue growth factor in the livers of non-viral hepatocellular carcinoma patients with metabolic risk factors","volume":"51","author":"Akahoshi","year":"2016","journal-title":"J. Gastroenterol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1002\/hep.27695","article-title":"Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n-3 and n-6 polyunsaturated fatty acids","volume":"61","author":"Arendt","year":"2015","journal-title":"Hepatology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"426","DOI":"10.21037\/jgo-21-274","article-title":"A narrative review of systemic treatment options for hepatocellular carcinoma: State of the art review","volume":"13","author":"Awosika","year":"2022","journal-title":"J. Gastrointest. Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jss.2013.07.001","article-title":"Stearoyl-CoA desaturase plays an important role in proliferation and chemoresistance in human hepatocellular carcinoma","volume":"186","author":"Bansal","year":"2014","journal-title":"J. Surg. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1200\/JCO.20.00437","article-title":"Genomic profiling of smoldering multiple myeloma identifies patients at a high risk of disease progression","volume":"38","author":"Bustoros","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"19695","DOI":"10.1073\/pnas.0609140103","article-title":"Molecular identification of microsomal acyl-CoA:glycerol-3-phosphate acyltransferase, a key enzyme in de novo triacylglycerol synthesis","volume":"103","author":"Cao","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.yexcr.2015.10.021","article-title":"Pathophysiology of lipid droplet proteins in liver diseases","volume":"340","author":"Carr","year":"2016","journal-title":"Exp. Cell Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1053\/j.gastro.2008.03.073","article-title":"Metabolic factors and risk of hepatocellular carcinoma by chronic Hepatitis B\/C infection: A follow-up study in taiwan","volume":"135","author":"Chen","year":"2008","journal-title":"Gastroenterology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/j.ajpath.2018.01.012","article-title":"\"Fatty acid binding protein 4 (Fabp4) overexpression in intratumoral hepatic stellate cells within hepatocellular carcinoma with metabolic risk factors.\"","volume":"188","author":"Chiyonobu","year":"2018","journal-title":"Am. J. Pathol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12967-018-1490-y","article-title":"CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading","volume":"16","author":"Chu","year":"2018","journal-title":"J. Transl. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1007\/s11605-011-1775-4","article-title":"High expression of CCL20 is associated with poor prognosis in patients with hepatocellular carcinoma after curative resection","volume":"16","author":"Ding","year":"2012","journal-title":"J. Gastrointest. Surg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00535-019-01633-2","article-title":"Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients","volume":"55","author":"Enooku","year":"2020","journal-title":"J. Gastroenterol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.cmet.2018.12.020","article-title":"Loss of BCAA catabolism during carcinogenesis enhances mTORC1 activity and promotes tumor development and progression","volume":"29","author":"Ericksen","year":"2019","journal-title":"Cell Metab."},{"key":"B15","doi-asserted-by":"crossref","first-page":"e0124544","DOI":"10.1371\/journal.pone.0124544","article-title":"Integrative Genomic Signatures of Hepatocellular Carcinoma Derived from Nonalcoholic Fatty Liver Disease","volume":"10","author":"Frades","year":"2015","journal-title":"PLoS ONE"},{"key":"B16","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1093\/hmg\/ddz300","article-title":"GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy","volume":"29","author":"Gao","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"D322","DOI":"10.1093\/nar\/gkj021","article-title":"The gene Ontology (go) project in 2006","volume":"34","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1007\/s12350-014-9908-2","article-title":"Survival analysis and regression models","volume":"21","author":"George","year":"2014","journal-title":"J. Nucl. Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1111\/j.0006-341x.2000.00337.x","article-title":"Time-dependent ROC curves for censored survival data and a diagnostic marker","volume":"56","author":"Heagerty","year":"2000","journal-title":"Biometrics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1002\/hep4.1182","article-title":"Metabolic risk factors are associated with non-Hepatitis B non-hepatitis C hepatocellular carcinoma in Taiwan, an endemic area of chronic Hepatitis B","volume":"2","author":"Huang","year":"2018","journal-title":"Hepatol. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","article-title":"KEGG as a reference resource for gene and protein annotation","volume":"44","author":"Kanehisa","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1002\/hep.29904","article-title":"Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification","volume":"68","author":"Kurebayashi","year":"2018","journal-title":"Hepatology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"Timer: A web server for comprehensive analysis of tumor-infiltrating immune cells","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"816472","DOI":"10.3389\/fonc.2022.816472","article-title":"Metabolic risks are increasing in non-B non-C early-stage hepatocellular carcinoma: A 10-year follow-up study","volume":"12","author":"Lin","year":"2022","journal-title":"Front. Oncol."},{"key":"B25","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2019-000501","article-title":"Identification of Fabp5 as an immunometabolic marker in human hepatocellular carcinoma","volume":"8","author":"Liu","year":"2020","journal-title":"J immunother cancer"},{"key":"B26","doi-asserted-by":"crossref","DOI":"10.1038\/s41417-022-00510-0","article-title":"\"Lipid-Related Fabp5 activation of tumor-associated monocytes fosters immune privilege via Pd-L1 expression on treg cells in hepatocellular carcinoma.\"","author":"Liu","year":"2022","journal-title":"cancer gene ther"},{"key":"B27","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":"B28","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1002\/hep.28584","article-title":"Global epidemiology of nonalcoholic fatty liver disease: Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Lonardo","year":"2016","journal-title":"Hepatology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1053\/j.gastro.2016.01.032","article-title":"The MBOAT7-TMC4 variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of European descent","volume":"150","author":"Mancina","year":"2016","journal-title":"Gastroenterology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1158\/1078-0432.CCR-18-1254","article-title":"The role of angiogenesis in hepatocellular carcinoma","volume":"25","author":"Morse","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.jhep.2011.10.005","article-title":"Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans","volume":"56","author":"Pihlajam\u00e4ki","year":"2012","journal-title":"J. Hepatol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12902-022-00980-1","article-title":"Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss","volume":"22","author":"Pouwels","year":"2022","journal-title":"BMC Endocr. Disord."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinforma."},{"key":"B35","doi-asserted-by":"publisher","first-page":"13974","DOI":"10.1074\/jbc.RA118.003541","article-title":"\"Perilipin 1 (Plin1) deficiency promotes inflammatory responses in lean adipose tissue through lipid dysregulation.\"","volume":"293","author":"Sohn","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1158\/1055-9965.EPI-19-0303","article-title":"The influence of metabolic syndrome on the risk of hepatocellular carcinoma in patients with chronic hepatitis B infection in mainland China","volume":"28","author":"Tan","year":"2019","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"Gepia: A web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/cdd.2015.121","article-title":"The transcription factor c-JUN\/AP-1 promotes HBV-related liver tumorigenesis in mice","volume":"23","author":"Trierweiler","year":"2016","journal-title":"Cell Death Differ."},{"key":"B40","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.gtc.2019.10.002","article-title":"Extrahepatic manifestations of nonalcoholic fatty liver disease","volume":"49","author":"Wattacheril","year":"2020","journal-title":"Gastroenterol. Clin. North Am."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e146","DOI":"10.1038\/nutd.2014.43","article-title":"Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity","volume":"5","author":"Wolfs","year":"2015","journal-title":"Nutr. Diabetes"},{"key":"B42","doi-asserted-by":"publisher","first-page":"111255","DOI":"10.1016\/j.biopha.2021.111255","article-title":"Crosstalk between PPARs and gut microbiota in NAFLD","volume":"136","author":"Wu","year":"2021"},{"key":"B43","doi-asserted-by":"publisher","first-page":"6642939","DOI":"10.1155\/2021\/6642939","article-title":"Identification of a potential PPAR-related multigene signature predicting prognosis of patients with hepatocellular carcinoma","volume":"2021","author":"Xu","year":"2021","journal-title":"PPAR Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"654517","DOI":"10.3389\/fgene.2021.654517","article-title":"Identification of key genes associated with the process of hepatitis B inflammation and cancer transformation by integrated bioinformatics analysis","volume":"12","author":"Zhang","year":"","journal-title":"Front. Genet."},{"key":"B45","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12944-021-01458-0","article-title":"TWIST2 and the PPAR signaling pathway are important in the progression of nonalcoholic steatohepatitis","volume":"20","author":"Zhang","year":"","journal-title":"Lipids Health Dis."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1066410\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T06:09:45Z","timestamp":1678082985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1066410\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,6]]},"references-count":45,"alternative-id":["10.3389\/fgene.2023.1066410"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1066410","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,6]]},"article-number":"1066410"}}