胃癌Smad4、CyclinDl和p21^(waf1)表达意义及其与生存的关系

Correlations of smad4,CyclinD1 and p21^(wafl) expression to prognosis of gastric carcinoma

目的研究Smad4、CyclinD1及p21^(waf1)在胃癌组织中的表达状况,分析其与临床病理特征及生存之间的关系。方法应用免疫组化S-P法,采用组织芯片技术,分析200例胃癌、56例癌旁组织中Smad4、CyclinD1和p21^(waf1)蛋白的表达。结果胃癌中Smad4、CyclinD1和p21^(waf1)蛋白的阳性表达率分别为67.0%、56.5%和59.5%。Smad4蛋白阳性表达率在低分化及弥漫型胃癌中较高分化及肠型胃癌降低(P<0.01);CyclinD1的表达水平在有淋巴结转移、低分化程度及弥漫型胃癌中高于无淋巴结转移、高分化及肠型胃癌者(P<0.05);p21^(waf1)蛋白的阳性表达率在低分化及弥漫型胃癌中较高分化及肠型胃癌者下降(P<0.05)。胃癌中Smad4与p21^(waf1)蛋白表达之间呈正相关性(r=0.179,P<0.05)。用Kaplan-Meier生存曲线经Log-rank检验发现,Smad4阳性表达者预后优于阴性表达者。结论胃癌中存在TGF-Smad4信号通路的异常,Smad4蛋白的异常表达可能导致p21^(waf1)蛋白的低表达,进而使p21^(waf1)对细胞G_1/S期的负性调控作用减弱,最终导致肿瘤的发生发展。Smad4蛋白高表达对胃癌患者是一个有利的预后因素,但尚不能作为一个独立的预后指标。

Objective To evaluate the expression patterns of Smad4, CyclinD1, p21^waf1 protein in gastric carcinoma and determine the relationship between Smad4, CyclinD1, p21^waf1, tumor clinicopathological features and patient survival as well. Methods The expression of Smad4, CyclinD1 and p21^waf1 protein was detected by S-P immunohistochemistry and tissue microarray in 200 specimens of primary human gastric carcinoma and 56 adjacent gastric tissues. Results The abnormal expression rates of Smad4, CyclinD1 and p21^waf1 protein in the tissues of gastric carcinoma were 67.0%, 56.5% and 59.5% respectively. Smad4 expression level was lower in poorly-differentiated and diffuse gastric carcinoma than in highly-differentiated and intestinal gastric carcinoma （P 〈0.01）. The higher expression of CyclinD1 was associated with lymph node metastasis, poorly-differentiated and diffuse gastric carcinoma （P 〈0.05）. The expression level of p21^waf1 in poorly-differentiated and diffuse gastric carcinoma was lower than in highlydifferentiated and intestinal gastric carcinoma （P 〈0.05）. Significant correlation were observed between Smad4 and p21^waf1 expression（r=0.179, P 〈0.05）. Smad4 positive expression was associated with favorable survival （P 〈0.05）. Conclusion Abnormal expressions of transforming growth factor-Smad4 signaling pathway occurs in gastric carcinoma. Smad4 may influence gastric carcinoma by regulating p21^waf1 and transition of cell cycle regulation G1/S and finally result in tumorigenesis. Positive expression of Smad4 is a favorable prognostic factor, but not an independent one in patients with gastric carcinoma.