title: Global DNA hypomethylation is associated with the development and poor prognosis of tongue squamous cell carcinoma.
abstract: BACKGROUND
  Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC.
  
  
  METHODS
  The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues.
  
  
  RESULTS
  We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009).
  
  
  CONCLUSIONS
  Global hypomethylation was an independent biomarker for the development and poor prognosis of TSCC.
authors.affiliation: Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Department of Dental Technology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: Cheng-Mei
authors.initials: CM
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Jiin-Tsuey
authors.initials: JT
authors.lastname: Cheng
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
authors.affiliation: Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Ting-Ying
authors.initials: TY
authors.lastname: Fu
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Huei-Han
authors.initials: HH
authors.lastname: Liou
authors.affiliation: Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Hui-Hwa
authors.initials: HH
authors.lastname: Tseng
authors.affiliation: Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Jang-Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Guan-Cheng
authors.initials: GC
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jyh-Seng
authors.initials: JS
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Department of Nursing, Yuh-Ing Junior College of Health Care and Management, Kaohsiung, Taiwan.
authors.forename: Yu-Yi
authors.initials: YY
authors.lastname: Hou
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Ta-Jung
authors.initials: TJ
authors.lastname: Weng
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Luo-Ping
authors.initials: LP
authors.lastname: Ger
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D063646:Carcinogenesis / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D044503:5-Methylcytosine
keywords: hypomethylation; immunohistochemistry; survival; tissue microarray; tongue squamous cell carcinoma