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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。
Objective: To investigate the effect of abnormal expression of serine-threonine kinase receptor-associated protein (STRAP) on gastric cancer cell differentiation. Methods: Totally 253 gastric cancer specimens collected from Department of Digestive Oncology, Cancer Hospital of Peking University from January 1991 to January 2009 were collected. At the same time, another 103 cases of gastric cancer tissues from the same patients were used as control to prepare tissue microarray. Immunohistochemistry was used to detect the expression of STRAP protein in gastric cancer tissues and paracancerous tissues. The relationship between the expression of STRAP protein and the clinicopathologic factors such as gastric cancer cell differentiation and clinical stage were analyzed. Kaplan-Meier survival analysis was used to investigate the relationship between STRAP protein expression and gastric cancer The expression of STRAP in gastric cancer SGC7901 cells was detected by Western blotting. The proliferation of SGC7901 cells was detected by MTT assay. The expression of STRAP in gastric cancer cells was detected by immunofluorescence staining To investigate the expression of pepsinogen C (PGC) in SGC7901 cells and analyze the activity of alkaline phosphatases (AKP) in STRAP overexpression cells. Results: The positive rate of STRAP protein in gastric cancer tissues was significantly lower than that in paracancer tissues [33.6% (75/223) vs 59.3% (51/86), P <0.01], and its expression level was closely related to the differentiation of gastric cancer cells (P <0.05). The patients with higher STRAP protein expression had longer survival time than those with low expression (P <0.05). The proliferation of SGC7901 cells was significantly decreased after overexpression of STRAP (P <0.05). The expression of PGC in gastric cancer cells was significantly increased (P <0.05), while the activity of AKP was significantly decreased (P <0.05). CONCLUSION: The expression of STRAP protein in gastric cancer is closely related to the differentiation of gastric cancer cells. It may be used as a molecular marker to assist in the judgment of the differentiation and prognosis of gastric cancer cells.