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目的明确转化生长因子β1(TGF-β1)及其受体基因和下游Smad基因家族成员在肠型胃癌中的表达变化与临床病理学特征及其预后的关系。方法在建立胃癌差异基因表达谱的基础上,确定胃癌及癌旁形态学正常组织中TGF-β1的mRNA表达水平存在明显差异,进一步利用组织微阵列和免疫组化染色分别检测了胃癌及癌旁形态学正常组织中TGF-β1蛋白表达水平。结果TGF-β1蛋白主要以细胞质着色为主,在90例胃癌组织中32例(36%)阳性表达,58例(64%)为阴性表达。进一步对不同分化程度的胃癌组织中TGF-β1蛋白的表达进行分析,结果表明在39例高中分化组织中23例(59%)呈阳性表达,而51例低分化胃癌中9例(18%)为阳性表达,差异有统计学意义(P<0·01)。进一步分析了TGF-βR-Ⅰ蛋白的表达,在74例胃癌组织中42例(57%)阳性表达,32例(43%)染色阴性。在38例高中分化组织中26例(68%)呈阳性表达,在36例低分化胃癌中16例(44%)阳性表达,差异有统计学意义(P<0·05)。对有随访资料的肠型胃癌的TGF-β1及TGF-βR-Ⅰ蛋白的表达情况与临床病理学特征进行分析。应用Kaplan-Meier法分析蛋白阳性和阴性表达组病例的生存时间,确定TGF-β1蛋白阳性表达组病例生存和预后明显好于TGF-β1阴性表达组病例(P=0·0058)。而TGF-βR-Ⅰ蛋白表达与生存和预后无明显关系(P=0·8453)。结论TGF-β1表达水平与胃癌的分化程度有关,表达阳性组病例的预后明显好于表达阴性组的病例,提示TGF-β1表达对中晚期胃癌的再分型和分类具有重要的临床意义。
Objective To investigate the relationship between the expression of transforming growth factor β1 (TGF-β1), its receptor gene and the downstream Smad gene family member in intestinal-type gastric cancer and its clinicopathological features and prognosis. Methods The expression of TGF-β1 mRNA in gastric cancer and adjacent normal tissues was determined based on the differential gene expression patterns of gastric cancer. The mRNA and protein expression of TGF-β1 in gastric cancer tissues and adjacent normal tissues were also determined. Tissue microarray and immunohistochemical staining were used to detect the expression of TGF- TGF-β1 protein expression in normal morphology. Results TGF-β1 protein was mainly expressed in cytoplasm, 32 (36%) were positive in 90 cases of gastric carcinoma and 58 (64%) were negative in TGF-β1. Furthermore, the expression of TGF-β1 in gastric cancer tissues with different degrees of differentiation was analyzed. The results showed that 23 cases (59%) were positive in 39 cases of high-differentiated tissues and 9 cases (18%) in 51 cases of poorly differentiated gastric cancer For the positive expression, the difference was statistically significant (P <0.01). Further analysis of the expression of TGF-βR-Ⅰ protein in 42 cases of gastric cancer tissues (57%) positive, 32 cases (43%) negative staining. 26 cases (68%) were positive in 38 cases of high differentiation tissues and 16 cases (44%) in 36 cases of poorly differentiated gastric carcinoma, the difference was statistically significant (P <0.05). The expression of TGF-β1 and TGF-βR-Ⅰ protein in intestinal-type gastric cancer with follow-up data and the clinicopathological features were analyzed. Kaplan-Meier method was used to analyze the survival time of the positive and negative protein expression groups. The survival and prognosis of TGF-β1-positive group were significantly better than that of TGF-β1-negative group (P = 0.0058). However, TGF-βR-Ⅰ protein expression had no significant relationship with survival and prognosis (P = 0.04545). Conclusion The expression of TGF-β1 is correlated with the differentiation of gastric cancer. The prognosis of patients with positive expression of TGF-β1 is significantly better than that of negative expression of TGF-β1, suggesting that TGF-β1 expression has important clinical significance in the re-classification and classification of advanced gastric cancer.