{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:40:52Z","timestamp":1760060452072,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education and Scientific Research in Algeria","award":["D00L04UN050220210001"],"award-info":[{"award-number":["D00L04UN050220210001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The undifferentiated nasopharyngeal cancer (NPC) is a multifactorial disease mainly due to Epstein-Barr Virus (EBV) infection. The transmembrane tyrosine kinase \u2018EphA2\u2019 and the protease \u2018Furin\u2019 are implicated in the EBV entry into epithelial cells and other physiological processes. To gain insights into the association of single-nucleotide polymorphisms (SNPs) rs4702 and rs6603883 (FURIN and EPHA2 genes, respectively) with the risk and prognosis of the NPC, the genotypes of 471 individuals (228 cases and 243 controls) were assessed alongside risk cofactors (sex, tobacco, alcohol, occupation, and recurrent Ear, Nose and Throat infections) and prognosis cofactors (Tumor stage, local invasion, lymph node involvement, and metastasis) using multivariable logistic regression. We found that only the rs4702 AG\/GG genotypes were statistically significantly associated with a reduced risk of cancer, both in the overall population and in men (approximately 50% reduction). The rs4702 GG genotype was also associated with a low frequency of local tumor invasion in the whole population (OR = 0.382, p = 0.017, co-dominant model, and OR = 0.409, p = 0.02, recessive model), but heterozygous women were associated with a higher lymph node involvement (OR = 3.53, p = 0.031, co-dominant model, and OR = 3.62, p = 0.02, overdominant model). The rs6603883 GG genotype was associated, in the dominant model, with distant metastasis in the whole population (OR = 2.5, p = 0.024), with advanced clinical stage in men (OR = 2.22, p = 0.034), and with advanced clinical stage and distant metastasis in patients under 49 years (OR = 3.13, p = 0.009, and OR = 5.15, p = 0.011, respectively). Additionally, men having the rs6603883 GA genotype were associated with lymph node invasion (OR = 2.22, p = 0.027, overdominant model). Our study is the first to demonstrate that FURIN and EPHA2 germline gene polymorphisms are associated with NPC risk (for rs4702) and prognosis (for both rs4702 and rs6603883), with sex-specific differences. These results need to be replicated and further investigated in other populations.<\/jats:p>","DOI":"10.3390\/ijms26178486","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Single-Nucleotide Polymorphisms on FURIN and EPHA2 Genes with the Risk and Prognosis of Undifferentiated Nasopharyngeal Cancer"],"prefix":"10.3390","volume":"26","author":[{"given":"Seddam","family":"Hares","sequence":"first","affiliation":[{"name":"Laboratory of Acquired and Constitutional Genetic Diseases (MAGECA), Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Faculty of Nature and Life Sciences, Batna 2 University, Batna 05000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Hamizi","sequence":"additional","affiliation":[{"name":"Laboratory of Acquired and Constitutional Genetic Diseases (MAGECA), Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Radiotherapy Department, Cancer Control Center (CLCC), Batna 05000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamza","family":"Rahab","sequence":"additional","affiliation":[{"name":"National Biotechnology Research Center (CRBt), Constantine 25016, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4677-7459","authenticated-orcid":false,"given":"Maewa Hibatouallah","family":"Bounneche","sequence":"additional","affiliation":[{"name":"National Biotechnology Research Center (CRBt), Constantine 25016, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Souhila","family":"Aouidane","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Epidemiology and Preventive Medicine Department, Benflis Touhami University Hospital, Batna 05000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Mansoura","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Clinical Oncology Department, Cancer Control Center (CLCC), Batna 05000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manel","family":"Denni","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Radiotherapy Department, Cancer Control Center (CLCC), Batna 05000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wissem","family":"Mallem","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Radiotherapy Department, Cancer Control Center (CLCC), Batna 05000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0431-7286","authenticated-orcid":false,"given":"Ghania","family":"Belaaloui","sequence":"additional","affiliation":[{"name":"Laboratory of Acquired and Constitutional Genetic Diseases (MAGECA), Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"},{"name":"Faculty of Medicine, Batna 2 University, Batna 05000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/S0140-6736(15)00055-0","article-title":"Nasopharyngeal Carcinoma","volume":"387","author":"Chua","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s10555-017-9693-x","article-title":"Progression of Understanding for the Role of Epstein-Barr Virus and Management of Nasopharyngeal Carcinoma","volume":"36","author":"Nakanishi","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1016\/j.ejca.2010.04.004","article-title":"Nasopharyngeal Carcinoma: The next Challenges","volume":"46","author":"Razak","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1158\/1055-9965.EPI-20-1702","article-title":"The Evolving Epidemiology of Nasopharyngeal Carcinoma","volume":"30","author":"Chang","year":"2021","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_5","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1158\/1055-9965.EPI-08-0461","article-title":"Age-Incidence Curves of Nasopharyngeal Carcinoma Worldwide: Bimodality in Low-Risk Populations and Aetiologic Implications","volume":"17","author":"Bray","year":"2008","journal-title":"Cancer Epidemiol Biomark. Prev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"vii308","DOI":"10.1093\/annonc\/mdq277","article-title":"Nasopharyngeal Carcinoma","volume":"21","author":"Chan","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20160270","DOI":"10.1098\/rstb.2016.0270","article-title":"Epstein\u2013Barr Virus Infection and Nasopharyngeal Carcinoma","volume":"372","author":"Tsao","year":"2017","journal-title":"Phil. Trans. R. Soc. B"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/path.1711650105","article-title":"Epstein-Barr Virus and Carcinomas: Undifferentiated Carcinomas but Not Squamous Cell Carcinomas of the Nasopharynx Are Regularly Associated with the Virus","volume":"165","author":"Niedobitek","year":"1991","journal-title":"J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(19)30956-0","article-title":"Nasopharyngeal Carcinoma","volume":"394","author":"Chen","year":"2019","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1016\/j.cell.2022.08.026","article-title":"Epstein-Barr Virus: Biology and Clinical Disease","volume":"185","author":"Damania","year":"2022","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1535-6108(04)00119-9","article-title":"Focus on Nasopharyngeal Carcinoma","volume":"5","author":"Lo","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/2281053a0","article-title":"Epstein-Barr Virus in Burkitt\u2019s Lymphoma and Nasopharyngeal Carcinoma. Antibodies to EBV Associated Membrane and Viral Capsid Antigens in Burkitt Lymphoma Patients","volume":"228","author":"Klein","year":"1970","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bu, G.-L., Xie, C., Kang, Y.-F., Zeng, M.-S., and Sun, C. (2022). How EBV Infects: The Tropism and Underlying Molecular Mechanism for Viral Infection. Viruses, 14.","DOI":"10.3390\/v14112372"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/s41564-017-0081-7","article-title":"Ephrin Receptor A2 Is a Functional Entry Receptor for Epstein\u2013Barr Virus","volume":"3","author":"Chen","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41564-017-0080-8","article-title":"Ephrin Receptor A2 Is an Epithelial Cell Receptor for Epstein\u2013Barr Virus Entry","volume":"3","author":"Zhang","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/femsre\/fuz023","article-title":"Epithelial Cell Infection by Epstein\u2013Barr Virus","volume":"43","author":"Chen","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5964","DOI":"10.1038\/s41467-020-19617-9","article-title":"Molecular Basis of EphA2 Recognition by gHgL from Gammaherpesviruses","volume":"11","author":"Su","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4863","DOI":"10.1242\/dev.125.24.4863","article-title":"Failure of Ventral Closure and Axial Rotation in Embryos Lacking the Proprotein Convertase Furin","volume":"125","author":"Roebroek","year":"1998","journal-title":"Development"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 Entry into Cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell Entry Mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/360358a0","article-title":"Inhibition of Furin-Mediated Cleavage Activation of HIV-1 Glycoprotein Gp160","volume":"360","author":"Hallenberger","year":"1992","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1002\/j.1460-2075.1992.tb05305.x","article-title":"Influenza Virus Hemagglutinin with Multibasic Cleavage Site Is Activated by Furin, a Subtilisin-like Endoprotease","volume":"11","author":"Vey","year":"1992","journal-title":"EMBO J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1099\/vir.0.007237-0","article-title":"Cleavage of Epstein-Barr Virus Glycoprotein B Is Required for Full Function in Cell-Cell Fusion with Both Epithelial and B Cells","volume":"90","author":"Sorem","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1158\/1055-9965.EPI-15-0144","article-title":"A GWAS Meta-Analysis and Replication Study Identifies a Novel Locus within CLPTM1L\/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry","volume":"25","author":"Bei","year":"2016","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/ng.601","article-title":"A Genome-Wide Association Study of Nasopharyngeal Carcinoma Identifies Three New Susceptibility Loci","volume":"42","author":"Bei","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tang, M., Lautenberger, J.A., Gao, X., Sezgin, E., Hendrickson, S.L., Troyer, J.L., David, V.A., Guan, L., Mcintosh, C.E., and Guo, X. (2012). The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1003103"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ajhg.2009.07.007","article-title":"Genome-Wide Association Study Reveals Multiple Nasopharyngeal Carcinoma-Associated Loci Within the HLA Region at Chromosome 6p21.3","volume":"85","author":"Tse","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/jhg.2009.49","article-title":"A Genome-Wide Association Study Identifies ITGA9 Conferring Risk of Nasopharyngeal Carcinoma","volume":"54","author":"Ng","year":"2009","journal-title":"J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41576-019-0127-1","article-title":"Benefits and Limitations of Genome-Wide Association Studies","volume":"20","author":"Tam","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1002\/jmv.27748","article-title":"FURIN Gene Variants (Rs6224\/Rs4702) as Potential Markers of Death and Cardiovascular Traits in Severe COVID-19","volume":"94","author":"Coto","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.schres.2018.02.040","article-title":"Schizophrenia-Associated Rs4702 G Allele-Specific Downregulation of FURIN Expression by miR-338-3p Reduces BDNF Production","volume":"199","author":"Hou","year":"2018","journal-title":"Schizophr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1111\/jcmm.17074","article-title":"The G to A Transformation of Rs4702 Polymorphism in 3\u2019UTR of FURIN Reduced the Risk of Radiotherapy-induced Cognitive Impairment in Glioma Patients","volume":"26","author":"Yang","year":"2022","journal-title":"J. Cell. Mol. Medi."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ma, X., Ma, Z., Jiao, X., and Hejtmancik, J.F. (2017). Functional Non-Coding Polymorphism in an EPHA2 Promoter PAX2 Binding Site Modifies Expression and Alters the MAPK and AKT Pathways. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-10117-3"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/aje\/kwg150","article-title":"Searching for Disease-Susceptibility Loci by Testing for Hardy-Weinberg Disequilibrium in a Gene Bank of Affected Individuals","volume":"158","author":"Lee","year":"2003","journal-title":"Am. J. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nrc.2016.92","article-title":"Epstein-Barr Virus: More than 50 Years Old and Still Providing Surprises","volume":"16","author":"Young","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Liang, C., Kan, J., Wang, J., Lu, W., Mo, X., and Zhang, B. (2024). Nasopharyngeal Carcinoma-Associated Inflammatory Cytokines: Ongoing Biomarkers. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1448012"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.stemcr.2021.02.010","article-title":"Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection","volume":"16","author":"Dobrindt","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.molcel.2020.04.022","article-title":"A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells","volume":"78","author":"Hoffmann","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s00439-015-1546-5","article-title":"A Genome-Wide Expression Quantitative Trait Loci Analysis of Proprotein Convertase Subtilisin\/Kexin Enzymes Identifies a Novel Regulatory Gene Variant for FURIN Expression and Blood Pressure","volume":"134","author":"Turpeinen","year":"2015","journal-title":"Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex Differences in Immune Responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/bies.201200099","article-title":"Sex Influences Immune Responses to Viruses, and Efficacy of Prophylaxis and Treatments for Viral Diseases","volume":"34","author":"Klein","year":"2012","journal-title":"Bioessays"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1385\/IR:34:3:177","article-title":"Sexual Dimorphism in Innate Immune Responses to Infectious Organisms","volume":"34","author":"Marriott","year":"2006","journal-title":"Immunol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41418-017-0051-x","article-title":"Sex Disparity in Cancer: Roles of microRNAs and Related Functional Players","volume":"25","author":"Bellenghi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1002\/tox.23791","article-title":"The Estrogen\/miR-338-3p\/ADAM17 Axis Enhances the Viability of Breast Cancer Cells via Suppressing NK Cell\u2019s Function","volume":"38","author":"Shi","year":"2023","journal-title":"Environ. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.3892\/or.2015.4195","article-title":"MicroRNA-338 Inhibits Migration and Proliferation by Targeting Hypoxia-Induced Factor 1\u03b1 in Nasopharyngeal Carcinoma","volume":"34","author":"Shan","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/mc.1057","article-title":"Elevated Furin Expression in Aggressive Human Head and Neck Tumors and Tumor Cell Lines","volume":"31","author":"Bassi","year":"2001","journal-title":"Mol. Carcinog."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10326","DOI":"10.1073\/pnas.191199198","article-title":"Furin Inhibition Results in Absent or Decreased Invasiveness and Tumorigenicity of Human Cancer Cells","volume":"98","author":"Bassi","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/ijc.10134","article-title":"Expression of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) in A2058 Melanoma Cells Is Associated with MMP-2 Activation and Increased Tumor Growth and Vascularization","volume":"98","author":"Sounni","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/ijc.30714","article-title":"The Proprotein Convertase Furin in Tumour Progression","volume":"141","author":"Jaaks","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101480","DOI":"10.1016\/j.tice.2020.101480","article-title":"Plac1 Promotes Nasopharyngeal Carcinoma Cells Proliferation, Migration and Invasion via Furin\/NICD\/PTEN Pathway","volume":"69","author":"Lin","year":"2021","journal-title":"Tissue Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.2147\/IJGM.S406802","article-title":"Identification of Serum miR-501-3p and miR-338-3p as Novel Diagnostic Biomarkers for Breast Cancer and Their Target Genes Associated with Immune Infiltration","volume":"16","author":"Yin","year":"2023","journal-title":"Int. J. Gen. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3233\/CBM-170339","article-title":"Downregulation of Tissue miR-338-3p Predicts Unfavorable Prognosis of Gastric Cancer","volume":"21","author":"Liu","year":"2017","journal-title":"Cancer Biomark."},{"key":"ref_54","first-page":"3662","article-title":"COA3 Overexpression Promotes Non-Small Cell Lung Cancer Metastasis by Reprogramming Glucose Metabolism","volume":"12","author":"Lin","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41564-024-01659-0","article-title":"Interferon-Induced Transmembrane Protein-1 Competitively Blocks Ephrin Receptor A2-Mediated Epstein-Barr Virus Entry into Epithelial Cells","volume":"9","author":"Yang","year":"2024","journal-title":"Nat. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1038\/ncomms7240","article-title":"Neuropilin 1 Is an Entry Factor That Promotes EBV Infection of Nasopharyngeal Epithelial Cells","volume":"6","author":"Wang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1038\/sj.onc.1210957","article-title":"Constitutive Activation of the Raf\u2013MAPK Pathway Causes Negative Feedback Inhibition of Ras\u2013PI3K\u2013AKT and Cellular Arrest through the EphA2 Receptor","volume":"27","author":"Menges","year":"2008","journal-title":"Oncogene"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cell.2008.03.011","article-title":"Eph-Ephrin Bidirectional Signaling in Physiology and Disease","volume":"133","author":"Pasquale","year":"2008","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ccr.2005.07.005","article-title":"A Conditional Feedback Loop Regulates Ras Activity through EphA2","volume":"8","author":"Macrae","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nrc2806","article-title":"Eph Receptors and Ephrins in Cancer: Bidirectional Signalling and Beyond","volume":"10","author":"Pasquale","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7050","DOI":"10.1158\/0008-5472.CAN-06-0004","article-title":"Disruption of EphA2 Receptor Tyrosine Kinase Leads to Increased Susceptibility to Carcinogenesis in Mouse Skin","volume":"66","author":"Guo","year":"2006","journal-title":"Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ccr.2009.04.009","article-title":"EphA2 Mediates Ligand-Dependent Inhibition and Ligand-Independent Promotion of Cell Migration and Invasion via a Reciprocal Regulatory Loop with Akt","volume":"16","author":"Miao","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41568-023-00634-x","article-title":"Eph Receptors and Ephrins in Cancer Progression","volume":"24","author":"Pasquale","year":"2024","journal-title":"Nat. Rev. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Toracchio, L., Carrabotta, M., Mancarella, C., Morrione, A., and Scotlandi, K. (2024). EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212191"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wang, X., Zou, Z., Deng, Z., Liang, D., Zhou, X., Sun, R., and Lan, K. (2017). Male Hormones Activate EphA2 to Facilitate Kaposi\u2019s Sarcoma-Associated Herpesvirus Infection: Implications for Gender Disparity in Kaposi\u2019s Sarcoma. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006580"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fei, Z., Hong, H., Xu, T., Xu, Y., Chen, J., Qiu, X., Ding, J., Feng, Y., Huang, C., and Li, L. (2023). Analysis of Risk Characteristics for Metachronous Metastasis in Different Period of Nasopharyngeal Carcinoma. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10641-8"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Su, W.-H., Yao Shugart, Y., Chang, K.-P., Tsang, N.-M., Tse, K.-P., and Chang, Y.-S. (2013). How Genome-Wide SNP-SNP Interactions Relate to Nasopharyngeal Carcinoma Susceptibility. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083034"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1186\/s12967-024-06011-y","article-title":"Spatial Transcriptomics Reveals Unique Metabolic Profile and Key Oncogenic Regulators of Cervical Squamous Cell Carcinoma","volume":"22","author":"Zhou","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"913","DOI":"10.6004\/jnccn.2017.0121","article-title":"Validation of the 8th Edition of the UICC\/AJCC Staging System for Nasopharyngeal Carcinoma From Endemic Areas in the Intensity-Modulated Radiotherapy Era","volume":"15","author":"Tang","year":"2017","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bursac, Z., Gauss, C.H., Williams, D.K., and Hosmer, D.W. (2008). Purposeful Selection of Variables in Logistic Regression. Source Code Biol. Med., 3.","DOI":"10.1186\/1751-0473-3-17"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","article-title":"A New Look at the Statistical Model Identification","volume":"19","author":"Akaike","year":"1974","journal-title":"IEEE Trans. Automat. Contr."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:37:03Z","timestamp":1760035023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":71,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178486"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178486","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}