{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:03:18Z","timestamp":1791770598171,"version":"4.3.4"},"reference-count":103,"publisher":"Bentham Science Publishers Ltd.","issue":"23","funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-65-00005"],"award-info":[{"award-number":["22-65-00005"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMC"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n<jats:title>Background:<\/jats:title>\n<jats:p>Non-alcoholic fatty liver disease (NAFLD) is a prevalent cause of chronic\nliver disease and encompasses a broad spectrum of disorders, including simple steatosis, steatohepatitis,\nfibrosis, cirrhosis, and liver cancer. However, due to the global epidemic of NAFLD, where invasive\nliver biopsy is the gold standard for diagnosis, it is necessary to identify a more practical method\nfor early NAFLD diagnosis with useful therapeutic targets; as such, molecular biomarkers could most\nreadily serve these aims. To this end, we explored the hub genes and biological pathways in fibrosis\nprogression in NAFLD patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>Raw data from microarray chips with GEO accession GSE49541 were downloaded from\nthe Gene Expression Omnibus database, and the R package (Affy and Limma) was applied to investigate\ndifferentially expressed genes (DEGs) involved in the progress of low- (mild 0-1 fibrosis score)\nto high- (severe 3-4 fibrosis score) fibrosis stage NAFLD patients. Subsequently, significant DEGs\nwith pathway enrichment were analyzed, including gene ontology (GO), KEGG and Wikipathway. In\norder to then explore critical genes, the protein-protein interaction network (PPI) was established and\nvisualized using the STRING database, with further analysis undertaken using Cytoscape and Gephi\nsoftware. Survival analysis was undertaken to determine the overall survival of the hub genes in the\nprogression of NAFLD to hepatocellular carcinoma.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>A total of 311 significant genes were identified, with an expression of 278 being upregulated\nand 33 downregulated in the high vs. low group. Gene functional enrichment analysis of these significant\ngenes demonstrated major involvement in extracellular matrix (ECM)-receptor interaction, protein\ndigestion and absorption, and the AGE-RAGE signaling pathway. The PPI network was constructed\nwith 196 nodes and 572 edges with PPI enrichment using a p-value &lt; 1.0 e-16. Based on this\ncut-off, we identified 12 genes with the highest score in four centralities: Degree, Betweenness,\nCloseness, and Eigenvector. Those twelve hub genes were CD34, THY1, CFTR, COL3A1,\nCOL1A1, COL1A2, SPP1, THBS1, THBS2, LUM, VCAN, and VWF. Four of these hub genes,\nnamely CD34, VWF, SPP1, and VCAN, showed significant association with the development of hepatocellular\ncarcinoma.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions:<\/jats:title>\n<jats:p>This PPI network analysis of DEGs identified critical hub genes involved in the progression\nof fibrosis and the biological pathways through which they exert their effects in NAFLD patients.\nThose 12 genes offer an excellent opportunity for further focused research to determine potential\ntargets for therapeutic applications.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0929867330666230516123028","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T05:20:27Z","timestamp":1684300827000},"page":"3631-3652","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Microarray-based Detection of Critical Overexpressed Genes in the\nProgression of Hepatic Fibrosis in Non-alcoholic Fatty Liver Disease:\nA Protein-protein Interaction Network Analysis"],"prefix":"10.2174","volume":"31","author":[{"given":"Ali","family":"Mahmoudi","sequence":"first","affiliation":[{"name":"Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad,\nIran"},{"name":"Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University\nof Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"De Vincentis","sequence":"additional","affiliation":[{"name":"Unit of Internal Medicine and Geriatrics, Universit\u00e0 Campus Bio-Medico di Roma, Fondazione Policlinico\nUniversitario Campus Bio-Medico di Roma, Via Alvaro del Portillo 200, Rome 00128, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tannaz","family":"Jamialahmadi","sequence":"additional","affiliation":[{"name":"Applied\nBiomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Applied\nBiomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran"},{"name":"Biotechnology Research\nCenter, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad,\nIran"},{"name":"School of Medicine, The University of Western Australia, Perth, Australia"},{"name":"Department of Biotechnology,\nSchool of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"e21463","DOI":"10.1097\/MD.0000000000021463","volume":"99","author":"Al-Qarni R.","year":"2020","unstructured":"Al-Qarni R.; Iqbal M.; Al-Otaibi M.; Al-Saif F.; Alfadda A.A.; Alkhalidi H.; Bamehriz F.; Hassanain M.; Validating candidate biomarkers for different stages of non-alcoholic fatty liver disease. 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