组织芯片技术检测DNA甲基转移酶1、人白细胞DR抗原α在肝细胞癌组织中的表达及临床意义

Gene expressions of DNA methyltransferase 1 and human leukocyte antigen-DRα in hepatocelluar carcinoma and their clinical significance

目的：探讨肝细胞癌（hepatocelluar carcinoma,HCC）组织中DNA甲基转移酶1（DNA methyltransferase 1,DNMT1）、人白细胞DR抗原α（HLA-DRα）的表达情况及其与临床病理特征、预后的关系。方法：选择1991年1月至2002年6月实施根治性肝切除、经病理证实的具备完整临床和随访资料的234例HCC患者,患者的随访时间为1.43-158.8个月[（30.04±26.61）个月],将患者的HCC石蜡组织制备成组织芯片,免疫组化检查采用Envision二步法,统计软件分析DNMT1和HLA-DRα的表达与临床病理特征、预后的关系。结果：HCC组织中DNMT1的阳性表达率为27.4%（64/234）,其阳性表达与门静脉癌栓、甲胎球蛋白（AFP）水平、TNM分期具有明显的相关性（P〈0.05）,与淋巴结侵犯无明显相关（P〉0.05）。HCC组织中HLA-DRα的阳性表达率为39.3%（92/234）,HLA-DRα的阳性表达与淋巴结侵犯、TNM分期具有明显的负相关性（P〈0.05）,与门静脉癌栓、AFP水平等无明显相关（P〉0.05）。DNMT1表达阳性的患者术后的中位存活时间为6.87个月,1年、3年、5年存活率分别是（38.89±6.63）%、（19.92±5.48）%、（17.58±5.31）%;DNMT1表达阴性患者的中位存活时间为40.33个月,1年、3年、5年存活率分别为（80.0±3.32）%、（51.63±4.30）%、（35.61±4.95）%（P〈0.001）。HLA-DRα表达阳性患者的术后中位存活时间为40.33个月,1年、3年、5年存活率分别为（81.01±4.41）%、（50.78±5.84）%、（38.04±6.09）%;HLA-DRα表达阴性患者的中位存活时间为12.43个月,1年、3年、5年存活率分别为（51.72±6.56）%、（26.44±5.91）%、（13.71±6.83）%（P〈0.01）。结论：DNMT1和HLA-DRα可能是影响HCC预后的重要分子,有望成为准确预测HCC预后的分子预后标记物。

Objective：To investigate the clinical significance and prognostic value of the expression of DNA methyhransferase 1 （DNMT1） and human leukocyte antigen-DRα （HLA-DRα） in hepatoeelluar carcinoma （HCC）. Methods： Paraffin-embedded tissues of 234 HCC underwent curative liver resection and 18 healthy adult liver samples from January 1991 to June 2002 in our department were used for the tissue microarray. Immunohistochemical technique （EnVisionTM） was applied to detect the expression of DNMT1 and HLA-DRα. The relationships between DNMT1, HLA-DRα and clinicopathological variables were analyzed statistically. Results： The rates of positive expression of DNMT1and HLA-DRα were 27.4 % and 39.3 %. The significant correlation was present between DNMT1 and portal vein tumor thrombus, alpha fetoprotein （AFP） level or TNM staging （P〈0.05） , but no significant correlation was present between DNMT1 and lymph node invasion. The significant correlation was present between HLA-DRα and lymph node invasion or TNM staging （P〈0.05）, but no significant correlation was present between HLA-DRα and lymph node invasion or AFP level （P〉0.05）. The postoperative median survival time was 6. 87 months and the 1-,3-,5-year cumulative survival rate was （38.89±6.63） % , （19.92±5.48）%, （17.58±5.31） % respectively in HCC with positive DNMTI, while the median survival time was 40. 33 months and the 1-,3-,5-year cumulative survival rate was （81.01±4. 41）% , （50. 78±5.84） %, （38.04±6.09） % respectively in patients with negative DNMT1 （P〈0.001）. The postoperative median survival time was 40. 33 months and the 1-,3-,5-year cumulative survival rate was （81.01±4.41）%, （50.78±5.84 %, （38.04±6.09）% respectively in HCC with positive HLA-DRα, while the median survival time was 12.43 months and the 1-, 3-, 5-year cumulative survival rate was （51.72±6.56）%,（26.44±5.91）%, （13.71±6.83）% （P〈0.01） respectively in patients with negative HLA-DRα （P 〈0.001）. Conclusion： DNMT1 and HLA-DRα are prognostic factors for HCC, which may be promising molecular prognostic factors for HCC.