CAJ | 학술논문

目的探讨DNA甲基转移酶(DNMTs)在肝门部胆管癌中的表达及其临床意义.方法收集1997年4月至2007年3月中山大学附属第一医院收治的111例肝门部胆管癌患者(胆管癌组)和39例胆总管囊肿患者(对照组)胆管组织标本,构建组织芯片,采用免疫组织化学方法检测DNMT1、DNMT3a、DNMT3b的蛋白表达水平；比较胆管癌组与对照组的胆管组织中DNMTs蛋白表达的差异；分析肝门部胆管癌组织中DNMTs蛋白表达与临床病理因素的关系,计数资料的比较采用x2检验或Fisher确切概率法,Kaplan-Meier法绘制生存曲线,生存情况分析采用Log-rank检验.结果胆管癌组的DNMT1和DNMT3b高表达率分别为54.1％ (60/111)和47.7％ (53/111),显著高于对照组的28.2％ (11/39)和23.1％ (9/39),两组比较,差异有统计学意义(x2=7.740,7.240,P＜0.05).DNMT1的高表达与Bismuth-Corlette分型、T分期存在明显相关性(x2=12.200,17.800,P＜0.05)；而DNMT3a在胆管癌组和对照组的高表达率比较,差异无统计学意义(x2=3.370,P＞0.05)；DNMT3b的高表达则只与Bismuth-Corlette分型存在明显相关性(x2=8.300,P＜0.05).111例患者中66例行肝门部胆管癌切除术,其中42例获得随访.DNMT1低表达者的术后中位生存时间为23.9个月,明显长于DNMT1高表达者的11.8个月(x2=3.980,P＜0.05).结论 DNMT1和DNMT3b高表达在肝门部胆管癌发生、发展中起重要作用；DNMT1的表达水平与肝门部胆管癌根治性切除术后生存时间明显相关,可望成为有价值的预测因子.
목적 탐토DNA갑기전이매(DNMTs)재간문부담관암중적표체급기림상의의.방법 수집1997년4월지2007년3월중산대학부속제일의원수치적111례간문부담관암환자(담관암조)화39례담총관낭종환자(대조조)담관조직표본,구건조직심편,채용면역조직화학방법검측DNMT1、DNMT3a、DNMT3b적단백표체수평；비교담관암조여대조조적담관조직중DNMTs단백표체적차이；분석간문부담관암조직중DNMTs단백표체여림상병리인소적관계,계수자료적비교채용x2검험혹Fisher학절개솔법,Kaplan-Meier법회제생존곡선,생존정황분석채용Log-rank검험.결과 담관암조적DNMT1화DNMT3b고표체솔분별위54.1％ (60/111)화47.7％ (53/111),현저고우대조조적28.2％ (11/39)화23.1％ (9/39),량조비교,차이유통계학의의(x2=7.740,7.240,P＜0.05).DNMT1적고표체여Bismuth-Corlette분형、T분기존재명현상관성(x2=12.200,17.800,P＜0.05)；이DNMT3a재담관암조화대조조적고표체솔비교,차이무통계학의의(x2=3.370,P＞0.05)；DNMT3b적고표체칙지여Bismuth-Corlette분형존재명현상관성(x2=8.300,P＜0.05).111례환자중66례행간문부담관암절제술,기중42례획득수방.DNMT1저표체자적술후중위생존시간위23.9개월,명현장우DNMT1고표체자적11.8개월(x2=3.980,P＜0.05).결론 DNMT1화DNMT3b고표체재간문부담관암발생、발전중기중요작용；DNMT1적표체수평여간문부담관암근치성절제술후생존시간명현상관,가망성위유개치적예측인자.
Objective To investigate the expression of DNA methyltransferases ( DNMTs) in hilar cholangiocarcinoma and its clinical significance.Methods A total of 150 samples of cholangetic tissues were collected from 111 patients with hilar cholangiocarcinoma ( cholangiocarcinoma group) and 39 patients with choledochocele ( control group) at the First Affiliated Hospital of Sun Yat-Sen University from April 1997 to March 2007.A tissue chip containing the samples of hilar cholangiocarcinoma and choledochocele was prepared.Expressions of DNMT1,DNMT3a and DNMT3b were detected by the immunohistochemical staining. Differences in the protein expressions of DNMTs in the cholangiocarcinoma group and the control group were compared,and the correlation between DNMTs protein expressions and clinicopathological features was analyzed.All data were analyzed by using the chi-square test or Fisher exact probability.The survival curve was drawn by using the Kaplan-Meier method and the survival rate was compared by using the Log-rank test.Results The rates of high protein expressions of DNMT1 and DNMT3b were 54.1％ (60/111) and 47.7％ (53/111) in the cholangiocarcinoma group, which were significantly higher than 28.2％ ( 11/39) and 23.1％ ( 9/39) in the control group　( x2 =7.740,7.240,P ＜0.05). The high protein expression of DNMT1 was correlated with-the Bismuth-Corlette classification and T staging of the tumor ( x2 =12.200, 17.800,P ＜0.05) ; there was no significant difference in the high protein expressions of DNMT3a in the cholangiocarcinoma group and the control group ( x2 =3.370.P ＞0.05 ) ; while the high protein expressions of DNMT3b was correlated with the Bismuth-Corlette classification (x2 =8.300,P ＜ 0.05 ),but not with the T staging. Sixty-six patients received hilar cholangiocarcinoma resection,and 42 of them were followed up.The median postoperative survival time of patients with low protein expression of DNMT1 was 23.9 months,which was significantly longer than 11.8 months of patients with high protein expression of DNMT1 (x2 =3.980,P ＜ 0.05).Conclusions DNMT1 and DNMT3b with high protein expression might play important roles in the carcinogenesis and development of hilar cholangiocarcinoma.There is an obvious relationship between the expression of DNMT1 and postoperative survival time of patients with hilar cholangiocarcinoma,and DNMT1 might be a valuable prognostic factor for hilar cholangiocarcinoma.