title: DNMT3a expression pattern and its prognostic value in lung adenocarcinoma.
abstract: DNA methyltransferases (DNMTs) are an important part of the methylation pathway that is highly correlated with the pathophysiology of cancers. Several studies have reported overexpression of DNMTs in human lung cancer, but none have compared the expression pattern to pathological features. In this study, we clarified the association of DNMT3a expression pattern with pathological features and prognosis of lung adenocarcinoma.
  
  
  
  135 cases of surgically resected lung adenocarcinoma specimens were used for DNMT3a immunohistochemistry (IHC). IHC score was determined by counting the number of positive nuclei. The ROC curve was drawn to determine the best cut-off point of the score; this was set at 57.5. Western blot also implemented and confirmed the specificity of the antibody. Correlations between expression pattern and clinicopathological features and prognosis were analyzed using chi-squared method and Cox proportional hazards model respectively.
  
  
  
  Seventy-nine of the 135 cases (58.5%) showed strong positive reactivity to anti-DNMT3a. In terms of histological subtypes, among invasive lung adenocarcinomas 41 out of 53 lepidic adenocarcinomas (77%) were strongly positive, while among the other histological subtypes only 23 out of 66 cases (34.8%) showed a positive reaction. Among non-invasive lung adenocarcinomas 15 out of 16 cases (93.8%) were strongly positive. The level of DNMT3a expression was associated with patient outcome, and patients with weak expression of DNMT3a had a poorer outcome than those with strong expression. Multivariate analysis also indicated that DNMT3a is an independent prognostic marker in lung adenocarcinoma.
  
  
  
  Our results indicate that DNMT3a expression in lung adenocarcinoma is associated with the histologically non-invasive type and lepidic subtype, and a favorable prognosis. We also showed that DNMT3a expression is an independent prognostic marker in lung adenocarcinoma. Since lack of DNMT3a is thought to facilitate tumor progression, DNMT3a might be clinically applicable as an indicator of favorable prognosis.
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Ryan Edbert
authors.initials: RE
authors.lastname: Husni
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Shiba-Ishii
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Iiyama
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shiozawa
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yunjung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kano
authors.affiliation: Department of Pathology, National Hospital Organization Ibarakihigashi National Hospital, The Center of Chest Diseases and Severe Motor and Intellectual Disabilities, Ibaraki, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Minami
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. Electronic address: junkano@md.tsukuba.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D000090205:DNA Methyltransferase 3A; D015254:DNA Modification Methylases / Q000378:metabolism; D057890:Epigenomics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C000717967:DNMT3A protein, human; D015254:DNA Modification Methylases; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: DNMT3a; Expression pattern; Lung adenocarcinoma; Prognosis