Retrospective Study
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World J Gastroenterol. Jul 7, 2014; 20(25): 8201-8208
Published online Jul 7, 2014. doi: 10.3748/wjg.v20.i25.8201
DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer
Xue-Yuan Cao, Hong-Xi Ma, Yan-Hong Shang, Mei-Shan Jin, Fei Kong, Zhi-Fang Jia, Dong-Hui Cao, Yin-Ping Wang, Jian Suo, Jing Jiang
Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Hong-Xi Ma, Mei-Shan Jin, Yin-Ping Wang, Division of Pathology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Yan-Hong Shang, Department of Oncology, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
Fei Kong, Zhi-Fang Jia, Dong-Hui Cao, Jing Jiang, Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Jiang J and Cao XY designed the study and carried out most of the study; Cao XY, Shang YH and Jiang J wrote the first draft of manuscript; Ma HX, Jin MS, and Wang YP analyzed pathological data; Kong F, Jia ZF and Cao DH collected patients’ clinical information; Jia ZF and Jiang J performed statistical analysis; Suo J provided valuable suggestions for the study.
Supported by Norman Bethune Program of Jilin University, No. 2013025; and National Natural Science Foundation of China, No. 81072369 and No. 81273065
Correspondence to: Jing Jiang, MD, PhD, Division of Clinical Epidemiology, First Hospital of Jilin University, No. 71 Xinming Dajie, Changchun 130021, Jilin Province, China. jiangjing19702000@jlu.edu.cn
Telephone: +86-431-81875408 Fax: +86-431-88782889
Received: January 13, 2014
Revised: February 8, 2014
Accepted: April 1, 2014
Published online: July 7, 2014
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: DNA methyltransferase, Prognosis, Gastric cancer, Expression, Helicobacter pylori

Core tip: Up to now, few studies investigated the expression of DNA methyltransferases (DNMTs) and the relationship between their expression and histopathology in gastric cancer. In this article, DNMT1, DNMT3a and DNMT3b expression has been investigated in 307 gastric cancer patients. The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNA methylation plays essential roles in the development of gastric cancer.