摘要
目的:探讨凝血因子Ⅶ(coagulation factorⅦ,FⅦ)和组织因子(tissue factor,TF)在大肠癌中的表达情况及其与临床病理因素的关系。方法:应用免疫组织化学法及Western blot对FⅦ蛋白在大肠癌组织中的表达情况进行研究;应用实时荧光定量PCR技术检测FⅦ和TF基因在45例结直肠癌患者癌及相应癌旁正常黏膜的表达。结果:(1)免疫组织化学及Western blot结果均显示FⅦ蛋白在大肠癌组织中存在异位高表达现象,癌旁正常黏膜不表达FⅦ蛋白;(2)免疫组织化学方法证实FⅦ蛋白定位表达于肿瘤细胞的胞浆和胞膜,大肠癌Ⅰ期、Ⅱ期、Ⅲ期及Ⅳ期的FⅦ表达阳性率分别为33.3%,40.0%,64.7%及80.0%(P=0.001);(3)实时荧光定量PCR方法显示大肠癌肝转移组FⅦmRNA表达明显高于非转移组,肝转移组表达量为5.33±2.88,无转移组为1.47±0.51(P=0.03),FⅦmRNA表达与肿瘤大小、分化、浸润深度、有无淋巴结转移及TNM分期无关,Spearman相关分析显示FⅦ在mRNA和蛋白水平表达呈一定的相关性,相关系数为0.58(P=0.03);(4)TF mRNA表达与大肠癌淋巴结转移、肝转移及TNM分期均有关,Logistic多因素回归分析影响肝转移的因素,结果表明TF表达是肝转移发生的重要因素(P=0.001)。结论:大肠癌组织可异源性地表达和分泌FⅦ,TF高表达是大肠癌发生肝转移的重要因素,肿瘤细胞周围高FⅦ的微环境可能促进大肠癌的转移。
Objective： To study the expression of coagulation factor Ⅶ （ F Ⅶ）/tissue factor （TF） complex in colorectal carcinoma （CRC） and its correlation with clinicopathologic factor. Methods： The expression of coagulation factor Ⅶ protein was studied by immunohistochemistry and Western blot. The expression of tissue factor and coagulation factor Ⅶ at the mRNA levels were evaluated by quantitative realtime RT-PCR in 45 cases of CRC. Results： （1） FⅦ overexpression was ectopicly detected in CRC specimens at protein level by immunohistochemistry and Western blot,but not in adjacent non-cancerous mucosa of colorectum; （2）FⅦ protein mainly localized in the cytoplasm of colon cancer cells. The positive ratios of FⅦ protein expression in stages Ⅰ , Ⅱ,Ⅲ and Ⅳ by immunohistochemistry assay were 33.3% , 40.0% ,64.7% and 80.0% respectively（ P = 0. 001 ） ; （3） The expression of FⅦ mRNA in CRC with hepatic metastasis was significantly higher than that in CRC without hepatic metastasis. The relative expression was 5.33 ＋ 2.88 and 1.47 ＋0.51 respectively（ P =0.03）. Overexpression FⅦ gene was unrelated with tumor size, differentiation, depth of invasion,lymph node metastasis and TNM staging. There existed some relation between the gene and protein level by Spearman correlation,r = 0.58 ,P = 0.003;（4） The expression of TF mRNA in CRC significantly correlated with lymph node metastasis, hepatic metastasis and TNM staging. The expression of tissue factor was a critical factor to predict liver metastasis by lo- gistic regression analysis（P = 0. 001 ）. Conclusion： Colorectal cancer can ectopicly synthesize coagulation factor Ⅶ. Tissue factor expression may play a role in the process of developing hepatic metastasis. The microenvironment of high dose FⅦ protein may promote tumor metastasis.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2009年第5期531-536,共6页
Journal of Peking University:Health Sciences
基金
国家自然科学基金(30872469)
国家自然科学基金青年基金(30801092)资助~~
关键词
结直肠肿瘤
凝血致活酶
因子Ⅶ
肿瘤转移
Colorectal neoplasms
Thromboplastin
Factor Ⅶ
Neoplasm metastasis
