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目的研究胃腺癌及癌旁组织中Smad4的表达、临床意义及对预后的判断价值。方法收集130例胃腺癌患者的手术切除标本共378份,其中取自癌组织130份,癌旁组织248份。采用免疫组织化学法检测胃组织芯片中Smad4的表达。结果癌旁正常胃黏膜均可见Smad4的正常表达,Smad4在肠上皮化生和不典型增生中正常表达率分别为83.3%和75.0%,在癌细胞中则为64.6%。Smad4在胃癌组织中的表达率显著低于癌旁黏膜组织,差异有统计学意义(P<0.05)。低分化癌细胞中Smad4蛋白表达率下降为42.2%,而高分化癌中仅为23.4%,Smad4表达与胃腺癌分化程度显著相关(P<0.05),而与其他临床病理参数无关。Kaplan-Meier分析显示,Smad4表达下降组3年生存率为35.0%,显著低于表达正常组的46.3%,差异有统计学意义(P<0.05)。Cox回归多因素分析显示,Smad4表达是一个独立的预后因素。结论Smad4异常表达在胃腺癌发生发展方面起重要作用,Smad4可作为评价胃癌预后的独立指标。
Objective To study the expression of Smad4 in gastric adenocarcinoma and its adjacent tissues and its clinical significance and prognostic value. METHODS: A total of 378 surgical specimens of 130 patients with gastric adenocarcinoma were collected, of which 130 were taken from cancer and 248 from paracancerous tissues. Immunohistochemistry was used to detect the expression of Smad4 in gastric tissue microarray. Results The normal expression of Smad4 was found in the adjacent normal gastric mucosa. The normal expression rates of Smad4 in intestinal metaplasia and atypical hyperplasia were 83.3% and 75.0%, respectively, and 64.6% in cancer cells. The expression of Smad4 in gastric cancer tissues was significantly lower than that in adjacent tissues (P <0.05). The expression of Smad4 in poorly differentiated cancer cells was decreased to 42.2%, compared with only 23.4% in well-differentiated cancers. Smad4 expression was significantly correlated with the differentiation of gastric adenocarcinoma (P <0.05), but not with other clinicopathological parameters. The Kaplan-Meier analysis showed that the 3-year survival rate of Smad4 decreased group was 35.0%, which was significantly lower than that of normal group (46.3%), the difference was statistically significant (P <0.05). Cox regression multivariate analysis showed that Smad4 expression was an independent prognostic factor. Conclusion The abnormal expression of Smad4 plays an important role in the development of gastric adenocarcinoma. Smad4 can be used as an independent index to evaluate the prognosis of gastric carcinoma.