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Lingual mucosa samples representative of normal tissue (week 0) and early (week 12) and advanced (week 28) tumorigenesis were harvested for microarray and methylated DNA immunoprecipitation sequencing (MeDIP-Seq). Combined analysis with Short Time-series Expression Miner (STEM), the Cytoscape plugin cytoHubba, and screening of differentially expressed genes enabled identification of 63 hub genes predominantly altered in the early stage rather than the advanced stage. Validation of microarray results was carried out using qRT-PCR. Of 63 human orthologous genes, 35 correlated with human oral squamous cell carcinoma. KEGG analysis showed \u201cpathways in cancer\u201d, involving 13 hub genes, as the leading KEGG term. Significant alterations in promoter methylation were confirmed at Tbp, Smad1, Smad4, Pdpk1, Camk2, Atxn3, and Cdh2. HDAC2, TBP, and EP300 scored \u226510 on Maximal Clique Centrality (MCC) in STEM profile 11 and were overexpressed in human tongue cancer samples. However, expression did not correlate with smoking status, tumor differentiation, or overall survival. These results highlight potentially useful candidate biomarkers for lingual cancer prevention, diagnosis, and treatment.<\/jats:p>","DOI":"10.1038\/s41598-018-31103-3","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T15:13:25Z","timestamp":1534432405000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Alterations of 63 hub genes during lingual carcinogenesis in C57BL\/6J mice"],"prefix":"10.1038","volume":"8","author":[{"given":"Hua","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsong","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyuan","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,8,22]]},"reference":[{"key":"31103_CR1","unstructured":"Global Burden of Disease Cancer Collaboration et al. 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