[关键词]
[摘要]
目的:探讨丝苏氨酸激酶受体相关蛋白(serine-threonine kinase receptor-associated protein,STRAP)异常表达对胃癌细胞分化的影响。方法:收集北京大学肿瘤医院消化肿瘤外科于1991年1月至2009年1月手术切除的胃癌标本253例,同时另取103例同批胃癌患者癌旁组织标本作为对照,制备组织芯片。采用免疫组化检测胃癌组织和癌旁组织中STRAP蛋白的表达,分析其表达与胃癌组织细胞分化、临床分期等临床病理因素的关系,采用Kaplan-Meier生存分析探讨STRAP蛋白的异常表达与胃癌患者预后的关系;将STRAP真核表达载体转染胃癌细胞SGC7901,采用Western blotting检测转染后胃癌SGC7901细胞中STRAP蛋白的表达情况,MTT法检测SGC7901细胞的增殖能力,免疫荧光染色法检测胃癌组织细胞分化相关蛋白胃蛋白酶原C(pepsinogen C,PGC)在SGC7901细胞中的表达情况,同时分析碱性磷酸酶(alkaline phosphatases,AKP)在STRAP过量表达细胞中的活性。结果:胃癌组织中STRAP蛋白的阳性表达率明显低于癌旁组织\[33.6%(75/223)vs 59.3%(51/86),P<0.01\],且其表达水平与胃癌细胞分化程度密切相关(P<0.05),STRAP蛋白表达较高的患者预后生存期明显长于低表达患者(P<0.05)。胃癌SGC7901细胞过表达STRAP蛋白后,其增殖能力明显减弱(P<0.05);胃癌组织细胞分化相关蛋白PGC表达水平显著升高(P<0.05),而AKP活性明显下降(P<0.05)。结论:STRAP蛋白在胃癌组织中的表达水平与胃癌组织细胞分化密切相关,其可能作为分子标志物对胃癌组织细胞分化程度和预后的辅助判断具有良好的临床价值。
[Key word]
[Abstract]
Objective:To explore effect abnormal expression of serine-threonine kinase receptor-associated protein (STRAP) on differentiation of gastriic cancer cells. Methods: Two hundred fifty three cases of surgically resected gastric carcinoma specimens in Department of Digestive Tumor Surgery, Tumor Hospital of Peking University during January 1991 to January 2009 were collected. At the same time, 103 cases of carcinoma adjacent tissue from the same lot of the patients with gastric carcinoma were collected as control. Tissue microarrays were prepared. Immuno histochemistry assay was used to detect expressions of STRAP protein in the gastric carcinoma tissues and the carcinoma adjacent tissues, and relationship between expressions of the STRAP protein and clinical pathological factors, namely differentiation of gastric carcinoma cells, clinical staging and so on was analyzed. Relationship between abnormal expression of STRAP protein and prognosis of the patients with gastric carcinoma was analyzed by Kaplan-Meier survival analysis. STRAP eukaryotic expression vectors were transfected into gastric carcinoma SGC7901 line cells. After the transfection, expressions of STRAP protein in the SGC7901 cells were examined by Western blotting, proliferation abilities of the SGC7901 cells were detected by MTT test, expressions of the gastric cancer cell differentiation associated-protein pepsinogen C (PGC) in the SGC7901 cells were checked by immuno fluorescence staining assay. Meanwhile activity of alkaline phosphatases (AKP)in the cells with excessive expression of STRAP was analyzed. Results: Positive expression rate of STRAP protein in the gastric carcinoma tissues was obviously lower than that in the carcinoma adjacent tissues (33.6% \[75/223\] vs 59.3% \[51/86\], P<001), and the expression level of STRAP was closely related to defferentiation grade of the gastric carcinoma cells (P<0.05), prognosis survival of the patients with high expression of STRAP protein was evidently longer than that of the patients with low expression of the protein (P<0.05). After overexpression of STRAP protein in the gastirc carcinoma SGC7901 cells, proliferation ability of the cells significantly attenuated (P<0.05), expression of the PGC obviously increased (P<0.05), and activity of the AKP evidently decreased (P<0.05). Conclusion: There could be a strong link between expression level of STRAP protein in the gastric carcinoma tissues and differentiation of the gastric carcinoma cells, the STRAP protein as a molecualr marker might have a good clinical value for differentiation grade of the gastric carcinoma cells and supplementary judgment of prognosis in the patients with gastric carcinoma.
[中图分类号]
[基金项目]
新疆生产建设兵团应用基础研究资助项目(No.2015AG015)