title: DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer.
abstract: OBJECTIVE
  To explore the alteration of DNA methyltransferase expression in gastric cancer and to assess its prognostic value.
  
  
  METHODS
  From April 2000 to December 2010, 227 men and 73 women with gastric cancer were enrolled in the study. The expression of DNA methyltransferases (DNMTs), including DNMT1, DNMT3a and DNMT3b, in the 300 cases of gastric carcinoma, of which 85 had paired adjacent normal gastric mucus samples, was evaluated by immunohistochemistry using a tissue microarray. Serum anti-Helicobacter pylori (H. pylori) IgG was detected by enzyme-linked immunosorbent assay (ELISA). The relationships between the above results and the clinicopathological characteristics were analyzed. Their prognostic value was evaluated using the Cox proportional hazards model.
  
  
  RESULTS
  In gastric cancer, expression of DNMTs was mainly seen in the nucleus. Weak staining was also observed in the cytoplasm. Expression of DNMT1, DNMT3a and DNMT3b in gastric cancer was significantly higher compared to that in the paired control samples (60.0% vs 37.6%, 61.2% vs 4.7%, and 94.1% vs 71.8%, P < 0.01). The overall survival rate was significantly higher in the DNMT3a negative group than in the DNMT3a positive group in gastric cancer patients (Log-rank test, P = 0.032). No significant correlation was observed between DNMT1 and DNMT3b expression and the overall survival time (Log-rank test, P = 0.289, P = 0.347). Multivariate regression analysis indicated that DNMT3a expression (P = 0.025) and TNM stage (P < 0.001), but not DNMT1 (P = 0.54) or DNMT3b (P = 0.62), were independent prognostic factors in gastric cancer. H. pylori infection did not induce protein expression of DNMTs.
  
  
  CONCLUSIONS
  The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNMT3a might play an important role in gastric carcinogenesis.
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Cao
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Ma
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Shang
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Mei-Shan
authors.initials: MS
authors.lastname: Jin
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Kong
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Zhi-Fang
authors.initials: ZF
authors.lastname: Jia
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Cao
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Suo
authors.affiliation: Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D014408:Biomarkers, Tumor / Q000032:analysis*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis*; D000090205:DNA Methyltransferase 3A; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000201:enzymology* / Q000382:microbiology / Q000401:mortality; D013997:Time Factors; D000097584:DNA Methyltransferase 3B
chemical_list: D000907:Antibodies, Bacterial; D014408:Biomarkers, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D007074:Immunoglobulin G; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human
keywords: DNA methyltransferase; Expression; Gastric cancer; Helicobacter pylori; Prognosis