Cao Xue-Yuan, Ma Hong-Xi, Shang Yan-Hong, Jin Mei-Shan, Kong Fei, Jia Zhi-Fang, Cao Dong-Hui, Wang Yin-Ping, Suo Jian, Jiang Jing
Xue-Yuan Cao, Jian Suo, Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
World J Gastroenterol. 2014 Jul 7;20(25):8201-8. doi: 10.3748/wjg.v20.i25.8201.
To explore the alteration of DNA methyltransferase expression in gastric cancer and to assess its prognostic value.
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.
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.
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.
探讨胃癌中DNA甲基转移酶表达的变化并评估其预后价值。
2000年4月至2010年12月，纳入227例男性和73例女性胃癌患者进行研究。采用组织芯片免疫组化法评估300例胃癌病例中DNA甲基转移酶（DNMTs），包括DNMT1、DNMT3a和DNMT3b的表达，其中85例有配对的相邻正常胃黏液样本。采用酶联免疫吸附测定（ELISA）检测血清抗幽门螺杆菌（H. pylori）IgG。分析上述结果与临床病理特征之间的关系。使用Cox比例风险模型评估其预后价值。
在胃癌中，DNMTs的表达主要见于细胞核。在细胞质中也观察到弱阳性染色。与配对对照样本相比，胃癌中DNMT1、DNMT3a和DNMT3b的表达显著更高（60.0%对37.6%、61.2%对4.7%、94.1%对71.8%，P<0.01）。胃癌患者中DNMT3a阴性组的总生存率显著高于DNMT3a阳性组（对数秩检验，P = 0.032）。未观察到DNMT1和DNMT3b表达与总生存时间之间存在显著相关性（对数秩检验，P = 0.289，P = 0.347）。多因素回归分析表明，DNMT3a表达（P = 0.025）和TNM分期（P<0.001），而非DNMT1（P = 0.54）或DNMT3b（P = 0.62），是胃癌的独立预后因素。幽门螺杆菌感染未诱导DNMTs的蛋白表达。
结果表明，DNMT3a表达是胃癌独立的不良预后指标。DNMT3a可能在胃癌发生中起重要作用。
