title: Immunohistochemical evaluation of Klotho and DNA methyltransferase 3a in oral squamous cell carcinomas.
abstract: Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma. Our results showed increased immune expression of DNMT3a, and decreased expression of Klotho in cells of the cancer tissues when compared with those in the dysplasia and healthy control samples. Chi-square tests complemented by adjusted residual analysis revealed significantly higher number of Klotho-positive and DNMT3a-negative cases in healthy controls, Klotho-negative and DNMT3a-negative cases in ODL, and Klotho-negative and DNMT3a-positive cases in OSCC when compared with the other types among the three groups (X2= 46.66, p < 0.001). Thus, downregulation of Klotho may be associated with the overexpression of DNMT3a in cancer tissues.
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Bhoj Raj
authors.initials: BR
authors.lastname: Adhikari
authors.affiliation: Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Uehara
authors.affiliation: Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Takai
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Harada
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Utsunomiya
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Chujo
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Division of Oral Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, 061-0293, Japan.
authors.forename: Mamata
authors.initials: M
authors.lastname: Shakya
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.affiliation: Division of Biochemistry, Department of Oral Biology, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Division of Oral Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Hokkaido, 061-0293, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagayasu
authors.affiliation: Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan.
authors.forename: Itsuo
authors.initials: I
authors.lastname: Chiba
authors.affiliation: Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. yoshi-ab@hoku-iryo-u.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Abiko
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D000090205:DNA Methyltransferase 3A; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C000717967:DNMT3A protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Anti-aging gene; DNMT3a; Dysplasia; Epigenetics; Immunohistochemistry; Klotho; OSCC