{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T03:22:21Z","timestamp":1775186541385,"version":"3.50.1"},"reference-count":51,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education-University and Research-MIUR, Progetto strategico di Eccellenza Dipartimentale","award":["#D15D18000410001"],"award-info":[{"award-number":["#D15D18000410001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatocellular adenomas (HAs) are tumors that can develop under different conditions, including in patients harboring a germline mutation in HNF1A. However, little is known about the pathogenesis of such disease. This work aims to better define what mechanisms lie under the development of this condition. Six HAs were sampled from the liver of a 17-year-old male affected by diabetes and multiple hepatic adenomatosis harboring the heterozygous pathogenic germline variant c.815G&gt;A, p.(Arg272His) in HNF1A, which has a dominant negative effect. All HAs were molecularly characterized. Four of them were shown to harbor a second somatic HNF1A variant and one had a mutation in the ARID1A gene, while no additional somatic changes were found in the remaining HA and normal parenchyma. A transcriptomic profile of the same HA samples was also performed. HNF1A biallelic mutations were associated with the up-regulation of several pathways including the tricarboxylic acid cycle, the metabolism of fatty acids, and mTOR signaling while angiogenesis, endothelial and vascular proliferation, cell migration\/adhesion, and immune response were down-regulated. Contrariwise, in the tumor harboring the ARID1A variant, angiogenesis was up-modulated while fatty acid metabolism was down-modulated. Histological analyses confirmed the molecular data. Independently of the second mutation, energetic processes and cholesterol metabolism were up-modulated, while the immune response was down-modulated. This work provides a complete molecular signature of HNF1A-associated HAs, analyzing the association between specific HNF1A variants and the development of HA while identifying potential new therapeutic targets for non-surgical treatment.<\/jats:p>","DOI":"10.3390\/ijms251910483","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T03:12:28Z","timestamp":1727665948000},"page":"10483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genomic and Transcriptomic Profile of HNF1A-Mutated Liver Adenomas Highlights Molecular Signature and Potential Therapeutic Implications"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2193-4577","authenticated-orcid":false,"given":"Angelo Corso","family":"Faini","sequence":"first","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Arruga","sequence":"additional","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Pinon","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit, Regina Margherita Children\u2019s Hospital, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Bracciam\u00e0","sequence":"additional","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Edoardo","family":"Vallone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorenza","family":"Mioli","sequence":"additional","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3308-7647","authenticated-orcid":false,"given":"Monica","family":"Sorbini","sequence":"additional","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Migliorero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-002X","authenticated-orcid":false,"given":"Alessandro","family":"Gambella","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"},{"name":"Division of Liver and Transplant Pathology, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damiano","family":"Carota","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Giraudo","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit, Regina Margherita Children\u2019s Hospital, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-7410","authenticated-orcid":false,"given":"Paola","family":"Cassoni","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-1846","authenticated-orcid":false,"given":"Silvia","family":"Catalano","sequence":"additional","affiliation":[{"name":"General Surgery 2U, Liver Transplantation Center, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-8885","authenticated-orcid":false,"given":"Renato","family":"Romagnoli","sequence":"additional","affiliation":[{"name":"General Surgery 2U, Liver Transplantation Center, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9437-9407","authenticated-orcid":false,"given":"Antonio","family":"Amoroso","sequence":"additional","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-3465","authenticated-orcid":false,"given":"Pier Luigi","family":"Calvo","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit, Regina Margherita Children\u2019s Hospital, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3375-6985","authenticated-orcid":false,"given":"Tiziana","family":"Vaisitti","sequence":"additional","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0632-5036","authenticated-orcid":false,"given":"Silvia","family":"Deaglio","sequence":"additional","affiliation":[{"name":"Immunogenetics and Transplant Biology Service, Azienda Ospedaliera-Universitaria Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"},{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1089\/dna.2005.24.661","article-title":"Functional Dissection of the HNF-1alpha Transcription Factor: A Study on Nuclear Localization and Transcriptional Activation","volume":"24","author":"Bratland","year":"2005","journal-title":"DNA Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12515","DOI":"10.1074\/jbc.275.17.12515","article-title":"Transcriptional Activation by Hepatocyte Nuclear Factor-1 Requires Synergism between Multiple Coactivator Proteins","volume":"275","author":"Soutoglou","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1093\/emboj\/20.8.1984","article-title":"Transcription Factor-Dependent Regulation of CBP and P\/CAF Histone Acetyltransferase Activity","volume":"20","author":"Soutoglou","year":"2001","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/jb\/mvh123","article-title":"Transcriptional Coactivators CBP and P300 Cooperatively Enhance HNF-1alpha-Mediated Expression of the Albumin Gene in Hepatocytes","volume":"136","author":"Dohda","year":"2004","journal-title":"J. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.2337\/diabetes.51.5.1409","article-title":"Hepatocyte Nuclear Factor-1alpha Recruits the Transcriptional Co-Activator P300 on the GLUT2 Gene Promoter","volume":"51","author":"Ban","year":"2002","journal-title":"Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sato, Y., Rahman, M.M., Haneda, M., Tsuyama, T., Mizumoto, T., Yoshizawa, T., Kitamura, T., Gonzalez, F.J., Yamamura, K.-I., and Yamagata, K. (2020). HNF1\u03b1 Controls Glucagon Secretion in Pancreatic \u03b1-Cells through Modulation of SGLT1. Biochim. Biophys Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165898"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/bs.apcsb.2017.07.004","article-title":"Probing the Protein-Protein Interaction Network of Proteins Causing Maturity Onset Diabetes of the Young","volume":"110","author":"Sneha","year":"2018","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/ng0495-418","article-title":"A Gene for Maturity Onset Diabetes of the Young (MODY) Maps to Chromosome 12q","volume":"9","author":"Vaxillaire","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1053\/j.gastro.2016.11.042","article-title":"Molecular Classification of Hepatocellular Adenoma Associates with Risk Factors, Bleeding, and Malignant Transformation","volume":"152","author":"Nault","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"HEP04","DOI":"10.2217\/hep-2017-0023","article-title":"Molecular Classification of Hepatocellular Adenomas: Impact on Clinical Practice","volume":"5","author":"Sutter","year":"2018","journal-title":"Hepatic Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"27117","DOI":"10.1016\/S0021-9258(19)61487-0","article-title":"Regulation of the Liver Fatty Acid-Binding Protein Gene by Hepatocyte Nuclear Factor 1alpha (HNF1alpha). Alterations in Fatty Acid Homeostasis in HNF1alpha-Deficient Mice","volume":"275","author":"Akiyama","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108018","DOI":"10.1016\/j.isci.2023.108018","article-title":"Dominant-Negative HNF1\u03b1 Mutant Promotes Liver Steatosis and Inflammation by Regulating Hepatic Complement Factor D","volume":"26","author":"Liu","year":"2023","journal-title":"iScience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.bbrc.2006.06.010","article-title":"Mutant HNF-1alpha and Mutant HNF-1beta Identified in MODY3 and MODY5 Downregulate DPP-IV Gene Expression in Caco-2 Cells","volume":"346","author":"Gu","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.1038\/s41467-020-19015-1","article-title":"Benchmarking of Cell Type Deconvolution Pipelines for Transcriptomics Data","volume":"11","author":"Powell","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s12020-019-02138-x","article-title":"Primary Hepatocellular Adenoma Due to Biallelic HNF1A Mutations and Its Co-Occurrence with MODY 3: Case-Report and Review of the Literature","volume":"67","author":"Fu","year":"2020","journal-title":"Endocrine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.2337\/dc12-0030","article-title":"Double Heterozygous Germline HNF1A Mutations in a Patient with Liver Adenomatosis","volume":"35","author":"Jeannot","year":"2012","journal-title":"Diabetes Care."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.gtc.2017.01.003","article-title":"Hepatocellular Adenomas: Morphology and Genomics","volume":"46","author":"Sempoux","year":"2017","journal-title":"Gastroenterol Clin. N. Am."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bbrc.2004.10.027","article-title":"Effect of Mutations in HNF-1alpha and HNF-1beta on the Transcriptional Regulation of Human Sucrase-Isomaltase in Caco-2 Cells","volume":"325","author":"Gu","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3138\/canlivj-2020-0010","article-title":"Hepatic Adenomatosis in a Young Woman with Non-Familial Maturity-Onset Diabetes of the Young Type 3","volume":"4","author":"Miles","year":"2021","journal-title":"Can. Liver J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1053\/j.gastro.2017.12.031","article-title":"A Young Patient with Diabetes and Liver Tumors","volume":"155","author":"Harryvan","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.jhep.2013.05.024","article-title":"Primary Hepatocellular Neoplasms in a MODY3 Family with a Novel HNF1A Germline Mutation","volume":"59","author":"Willson","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1055\/s-0033-1341519","article-title":"Maturity-Onset Diabetes of the Young and Hepatic Adenomatosis\u2014Characterisation of a New Mutation","volume":"121","author":"Iwen","year":"2013","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/j.gastro.2003.07.012","article-title":"Familial Liver Adenomatosis Associated with Hepatocyte Nuclear Factor 1alpha Inactivation","volume":"125","author":"Bacq","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1111\/liv.14235","article-title":"Diagnosis of Hepatocellular Adenoma in Men before Onset of Diabetes in HNF1A-MODY: Watch out for Winkers","volume":"39","author":"Haring","year":"2019","journal-title":"Liver Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.2337\/db09-1819","article-title":"Spectrum of HNF1A Somatic Mutations in Hepatocellular Adenoma Differs from That in Patients with MODY3 and Suggests Genotoxic Damage","volume":"59","author":"Jeannot","year":"2010","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/hep.23362","article-title":"Loss of Hepatocyte Nuclear Factor 1alpha Function in Human Hepatocellular Adenomas Leads to Aberrant Activation of Signaling Pathways Involved in Tumorigenesis","volume":"51","author":"Pelletier","year":"2010","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14437","DOI":"10.1074\/jbc.M610725200","article-title":"HNF1alpha Inactivation Promotes Lipogenesis in Human Hepatocellular Adenoma Independently of SREBP-1 and Carbohydrate-Response Element-Binding Protein (ChREBP) Activation","volume":"282","author":"Rebouissou","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1111\/liv.15066","article-title":"Hepatocellular Adenoma with a Double Mutation HNF1A and IDH1 in a Patient with Ollier Disease","volume":"41","author":"Cappellen","year":"2021","journal-title":"Liver Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bbrc.2017.10.174","article-title":"Q511L Mutation of HNF1\u03b1 in Hepatocellular Carcinoma Suppresses the Transcriptional Activity and the Anti-Tumor Effect of HNF1\u03b1","volume":"495","author":"Ding","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","first-page":"786","article-title":"Hepatic Adenomas in Patients 60 and Older Are Enriched for HNF1A Inactivation and Malignant Transformation","volume":"46","author":"Yasir","year":"2022","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humpath.2018.08.004","article-title":"Somatic HNF1A Mutations in the Malignant Transformation of Hepatocellular Adenomas: A Retrospective Analysis of Data from MSK-IMPACT and TCGA","volume":"83","author":"Hechtman","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1159\/000510215","article-title":"Malignant Transformation of an HNF1a-Inactivated Hepatocellular Adenoma to Hepatocellular Carcinoma","volume":"14","author":"Hepkema","year":"2020","journal-title":"Case Rep. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4047","DOI":"10.1074\/jbc.M114.597229","article-title":"Inhibition of PCSK9 Transcription by Berberine Involves Down-Regulation of Hepatic HNF1\u03b1 Protein Expression through the Ubiquitin-Proteasome Degradation Pathway","volume":"290","author":"Dong","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100339","DOI":"10.1016\/j.xgen.2023.100339","article-title":"Human Gain-of-Function Variants in HNF1A Confer Protection from Diabetes but Independently Increase Hepatic Secretion of Atherogenic Lipoproteins","volume":"3","author":"DeForest","year":"2023","journal-title":"Cell Genom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.gendis.2022.05.029","article-title":"Hepatocyte Nuclear Factor 1A Suppresses Innate Immune Response by Inducing Degradation of TBK1 to Inhibit Steatohepatitis","volume":"10","author":"He","year":"2023","journal-title":"Genes Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1080\/15548627.2022.2110728","article-title":"HNF1A Regulates the Crosstalk between Innate Immune Responses and MAFLD by Mediating Autophagic Degradation of TBK1","volume":"19","author":"Qin","year":"2023","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s00125-008-1168-8","article-title":"Early Loss of Mammalian Target of Rapamycin Complex 1 (mTORC1) Signalling and Reduction in Cell Size during Dominant-Negative Suppression of Hepatic Nuclear Factor 1-Alpha (HNF1A) Function in INS-1 Insulinoma Cells","volume":"52","author":"Farrelly","year":"2009","journal-title":"Diabetologia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1007\/s10495-011-0641-x","article-title":"Rapamycin Protects against Dominant Negative-HNF1A-Induced Apoptosis in INS-1 Cells","volume":"16","author":"Farrelly","year":"2011","journal-title":"Apoptosis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104374","DOI":"10.1016\/j.ejmg.2021.104374","article-title":"A Novel COLEC10 Mutation in a Child with 3MC Syndrome","volume":"64","author":"Migliorero","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A Web Server for Functional Enrichment Analysis and Functional Annotation of Gene Lists (2021 Update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Huang, D.W., Sherman, B.T., Tan, Q., Collins, J.R., Alvord, W.G., Roayaei, J., Stephens, R., Baseler, M.W., Lane, H.C., and Lempicki, R.A. (2007). The DAVID Gene Functional Classification Tool: A Novel Biological Module-Centric Algorithm to Functionally Analyze Large Gene Lists. Genome Biol., 8.","DOI":"10.1186\/gb-2007-8-9-r183"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Supek, F., Bo\u0161njak, M., \u0160kunca, N., and \u0160muc, T. (2011). REVIGO Summarizes and Visualizes Long Lists of Gene Ontology Terms. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021800"},{"key":"ref_43","unstructured":"Le Cao, K.-A., Rohart, F., Gonzalez, I., Dejean, S., Bartolo, F., Monget, P., Coquery, J., Yao, F., and Liquet, B. (2016). mixOmics: Omics Data Integration Project, mixOmics. R Package Version 6.1.1."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., and Ma\u2019ayan, A. (2013). Enrichr: Interactive and Collaborative HTML5 Gene List Enrichment Analysis Tool. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-128"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex Heatmaps Reveal Patterns and Correlations in Multidimensional Genomic Data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1093\/bioinformatics\/btu393","article-title":"Circlize Implements and Enhances Circular Visualization in R","volume":"30","author":"Gu","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). Ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust Enumeration of Cell Subsets from Tissue Expression Profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Becht, E., Giraldo, N.A., Lacroix, L., Buttard, B., Elarouci, N., Petitprez, F., Selves, J., Laurent-Puig, P., Saut\u00e8s-Fridman, C., and Fridman, W.H. (2016). Erratum to: Estimating the Population Abundance of Tissue-Infiltrating Immune and Stromal Cell Populations Using Gene Expression. Genome. Biol., 17.","DOI":"10.1186\/s13059-016-1113-y"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-1-0716-0327-7_17","article-title":"EPIC: A Tool to Estimate the Proportions of Different Cell Types from Bulk Gene Expression Data","volume":"2120","author":"Racle","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Aran, D., Hu, Z., and Butte, A.J. (2017). xCell: Digitally Portraying the Tissue Cellular Heterogeneity Landscape. Genome. Biol., 18.","DOI":"10.1186\/s13059-017-1349-1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10483\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:06:21Z","timestamp":1760112381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,29]]},"references-count":51,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910483"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910483","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,29]]}}}