【摘要】 目的:分析胃癌组织及细胞株中Fascin-1蛋白表达的临床病理及预后意义。方法:从日本理化研究所获得胃癌细胞株MKN28、AGS、MKN45和KATO-Ⅲ。收集日本富山大学医学部1993-02-01-2006-10-01胃癌组织455例。利用实时PCR、蛋白质印迹法杂交或免疫组化检测胃癌细胞株(MKN28、AGS、MKN45和KATO-Ⅲ)和胃癌组织中Fascin-1mRNA和蛋白的表达,分析胃癌组织中Fascin-1蛋白表达与临床病理特征和预后的关系。结果:Fascin-1蛋白主要定位在胃癌细胞株的细胞质中,在MKN28和MKN45细胞株中呈强表达,在AGS和KATO-Ⅲ细胞中弱表达。胃癌组织中Fascin-1mRNA表达水平显著高于癌旁正常黏膜组织,t=5.267,P<0.001;Fascin-1蛋白表达与胃癌肿块大小(rs=0.116,P<0.001)、侵袭深度(rs=0.177,P<0.001)、淋巴管侵袭(rs=0.190,P=0.005)、静脉侵袭(rs=0.131,P=0.003)、淋巴结转移(rs=0.141,P=0.013)和TNM分期(rs=0.174,P<0.001)呈正相关。Cox风险比率回归模型显示,年龄(P<0.001)、侵袭深度(P<0.001)、淋巴管侵袭(P<0.001)、淋巴结转移(P<0.001)、TNM分期(P<0.001)和Lauren分型(P=0.003)为独立的预后因素。结论:Fascin-1蛋白表达在胃癌细胞株的侵袭转移过程中发挥重要作用,Fascin-1蛋白表达上调参与胃癌发生和演进过程,可以作为胃癌恶性程度和预后判断的有效分子标志。更多还原

【Abstract】 OBJECTIVE:To observe the clinicopathological and prognostic significance of Fascin-1expression in gastric carcinoma.METHODS:Gastric carcinoma cell lines,MKN28,AGS,MKN45 and KATO-Ⅲ were obtained from the Japanese Physical and Chemical Institute.Gastric carcinomas(n=455)were collected from the department of Medicine,University of Toyama between 1993 and 2006.We examined Fascin-1expression in gastric carcinoma cell(MKN28,AGS,MKN45 and KATO-Ⅲ)and tissue by real-time PCR,immunohistochemistry and Western blot.Fascin-1expression was compared with clinicopatholgoical parameters and prognosis of gastric cancer.RESULTS:Fascin-1protein was localized in the cytoplasm of gastric carcinoma cell lines and showed its strong expression in MKN28 and MKN45,weak or absent in AGS and KATO-Ⅲ.Fascin-1mRNA was lowly expressed in gastric carcinoma,compared with matched non-neoplastic mucosa(t=5.267,P<0.001).Fascin-1protein expression was positively correlated with tumor size(rs=0.116,P<0.001),depth of invasion(rs=0.177,P<0.001),lymphatic(rs=0.190,P=0.005)and venous(rs=0.131,P=0.003)invasion,lymph node metastasis(rs=0.141,P=0.013)and TNM staging(rs=0.174,P<0.001).Cox’s proportional risk analysis showed that age(P<0.001),depth of invasion(P<0.001),lymphatic invasion(P<0.001),lymph node metastasis(P<0.001),TNM staging(P<0.001)and Lauren’s classification(P=0.003)were independent factors for the survival of the patients with gastric cancer.CONCLUSIONS:Fascin-1overexpression plays an important role in the invasion and metastasis of gastric carcinoma cells.Up-regulated Fascin-1expression may be involved in the tumorigenesis and progression of gastric cancer and employed to indicate the aggressiveness and worse prognosis of gastric cancer.更多还原