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组织因子/凝血因子VII复合物在结直肠癌中的异位表达及临床意义

[Ectopic expression and clinical significance of tissue factor/coagulation factor VII complex in colorectal cancer].

作者信息

Tang Jian Qiang, Fan Qing, Wan Yuan Lian, Liu Yu Cun, Wang Xin, Wu Tao, Pan Yi Sheng, Wu Wen Han, Zhu Jing

机构信息

Department of General Surgery, Peking University First Hospital, Beijing 100034, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2009 Oct 18;41(5):531-6.

Abstract

OBJECTIVE

To study the expression of coagulation factor VII(FVII)/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 logistic 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.

摘要

目的

研究凝血因子VII(FVII)/组织因子(TF)复合物在结直肠癌(CRC)中的表达及其与临床病理因素的相关性。

方法

采用免疫组织化学和蛋白质印迹法研究凝血因子VII蛋白的表达。应用定量实时逆转录聚合酶链反应(RT-PCR)检测45例CRC组织中组织因子和凝血因子VII的mRNA表达水平。

结果

(1)免疫组织化学和蛋白质印迹法在CRC标本中均检测到FVII蛋白异位过表达,而在结直肠非癌旁黏膜中未检测到;(2)FVII蛋白主要定位于结肠癌细胞的细胞质中。免疫组织化学检测I、II、III和IV期FVII蛋白表达的阳性率分别为33.3%、40.0%、64.7%和80.0%(P=0.001);(3)有肝转移的CRC中FVII mRNA表达明显高于无肝转移者,相对表达量分别为5.33±2.88和1.47±0.51(P=0.03)。FVII基因过表达与肿瘤大小、分化程度、浸润深度、淋巴结转移及TNM分期无关。Spearman相关性分析显示基因水平与蛋白水平存在一定相关性,r=0.58,P=0.003;(4)CRC中TF mRNA表达与淋巴结转移、肝转移及TNM分期显著相关。经Logistic回归分析,组织因子表达是预测肝转移的关键因素(P=0.001)。

结论

结直肠癌可异位合成凝血因子VII。组织因子表达可能在肝转移发生过程中起作用。高剂量FVII蛋白的微环境可能促进肿瘤转移。

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