分化抑制蛋白Id-1 在胃癌分化中的表达及作用

目的:研究Id- 1 蛋白与肿瘤分化程度的关系，选取临床病理分化程度诊断明确的胃癌组织芯片作为主要研究对象，确定Id- 1 蛋白在胃癌组织中的分布状况及该蛋白与胃癌病理学分级（分化程度）的相关性；利用体外实验模型，通过诱导分化，改变胃癌细胞的分化状态，进一步研究Id- 1 蛋白在体外是否随着胃癌细胞分化程度的改变而改变，确定Id- 1 蛋白在胃癌分化中的作用。方法:通过免疫组织化学法检测Id- 1 蛋白、Ki-67抗原在胃癌组织芯片表达；通过形态观察、细胞化学染色（PAS ）观察丁酸钠（sodium butyrate，NaB）对人低分化胃癌细胞MGC803 诱导分化，利用细胞免疫化学染色、Western-blot研究诱导分化前后Id- 1蛋白表达的改变。结果:胃癌组织中Id- 1 蛋白检测总阳性率为88.8% ，Id- 1 蛋白在高、中、低分化癌中阳性率分别为77.4% 、97.0% 、92.0% ，有显著性差异（P<0.001）；Ki-67抗原的总阳性表达率达78.7% ，在高、中、低分化癌中阳性率分别为64.5% 、90.9% 、80.0% ，有显著性差异（P<0.001）；组间比较Id- 1 蛋白与Ki-67抗原表达呈正相关。NaB 在体外作用于MGC803 细胞后细胞体积变大，核浆比变小，伸展状态好，细胞中PAS 阳性物质显著减少，出现分化状态改善的现象，分化后的MGC803 细胞内Id- 1 蛋白表达减少。结论:Id- 1 蛋白表达与胃癌分化程度呈负相关，可作为辅助诊断胃癌分化的标记物。 

The Effect of Id-1 in Differentiation of Gastric Carcinoma

Objective: To study the role of Id-1 protein in the differentiation of gastric carcinoma.Methods:Tissue chip and immunohistochemical staining were used to detect Id- 1 and Ki-67expression in tumor tissues. MGC803 cells were ex -posed to differentiation-inducing agents (sodium butyrate, NaB). The morphological changes and PAS staining were adopt-ed to confirm differentiation. Id- 1 expression of MGC 803 was assayed by immunocytochemistry and Western blot. Results: The total positive rate of Id- 1 in 89specimens of gastric cancer tissues was 88.8% , and the positive rates were77.4% ,97% and 92% in highly, medium and poorly differentiated carcinoma, respectively, with a significant difference. The positive rate of Ki- 67antigen was 78.7% in all samples. The positive rates of Ki-67antigen in highly, medium, and poorly differentiat-ed carcinoma were 64.5%,90.9% and 80%, respectively, with a statistical significance. Id-1 protein expression was positive -ly correlated with Ki-67antigen expression. Exposed to NaB, the MGC803 cells were obviously improved on the degree of cellular differentiation. The cells became larger, the nuclear cytoplasm ratio was decreased and immunocytochemistry showed less PAS staining. The expression of Id- 1 was sharply decreased as the cells became more differentiated. Conclusion: The expression of Id- 1 in gastric cancer is negatively correlated with differentiation. Id- 1 protein can be an index for grading of gastric cancer.