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Archive > Volume 23 Issue 3 > 2016,23(3):326-334. DOI:10.3872/j.issn.1007-385X.2016.03.006 Prev Next
Prompt Report
Relationship of polymorphism interaction of α1-antitypsin and tissue factor pathway inhibitor genes with invasion and metastasis of colorectal carcinoma
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Abstract:
Objective:To investigate polymorphism interaction of α1-antitypsin (α1-AT) gene exon 5 and tissue factor pathway inhibitor (TFPI) gene T287C and relationship of the gene polymorphism interation with invasion and metastasis of colon carcinoma. Methods: Each of one hundred eighty patients diagnosed as the TNM Ⅰ,Ⅱ, Ⅲ or Ⅳ stage colon carcinoma received and treated by the First Hospital affiliated to Xinxiang Medical University Henan Province during July 2011 to July 2015 were selected. One hundred eighty patients with the TNM 0 stage colon carcinoma who without involvement of reginol lymph nodes and distant metastasis were selected as control group. Polymorphisms of the both genes in peripheral blood leukocytes of the patients in each group were tested with PCR-RFLP assay. Hardy-Weinberg equilibrium tests were used to analyze the population representativeness of the samples. Polymorphism interaction of the both genes was examed with Khoury and Wagener model. Expressions of the α1-AT and TFPI proteins in serum were tested by ELISA assay. Scratch test and Transwell invasion assay were used to detect the effect of the α1-AT and TFPI on migration and invation abilities of the human colon carcinoma SW480 line cells respectively. Expression levels of cell trypsin, tissue factor (TF) and protease-activated receptor -2 (PAR-2) were tested with Western blotting assay. Results: Risks of invasion and metastasis of the colorectal cancer in the patients with genotypes of α1-AT(MZ), α1-AT(ZZ), TFPI (TC) and TFPI (CC) significantly increased, furthermore there was a positive interaction between α1-AT (MZ) and TFPI (TC), α1-AT (MZ) and TFPI (CC), α1-AT (ZZ) and TFPI (TC), and α1-AT (ZZ) and TFPI (CC) at all (all γ＞1 ). Expressions of the α1-AT and TFPI proteins in the patients with TNM Ⅰ,Ⅱ, Ⅲ,Ⅳ stage were significantly lower than that in the patients with TNM 0 stage, and expressions of serum α1-AT and TFPI proteins among the patients with TNM Ⅰ,Ⅱ, Ⅲ and Ⅳ stage were also obviously different ( P<0.01). In the same group, exoressions of serum α1-AT and TFPI proteins in the patients with mutant genotype were significantly lower than those in the patients with wild genotype (P<001). Cell culture in vitro experiments shown that α1-AT obviously inhibited exoression of cell trypsin in the SW480 cells, but TFPI inhibited expression of TF evidently. As well as both of them could significantly decrease expression of PAR-2 protein and, migration and invasion abilities of the cells. Conclusion: All genotypes of α1-AT (MZ), α1-AT (ZZ), TFPI (TC) and TFPI (CC) might be risk factors for invasion and metastasis of the colon carcinoma. Polymorphisms and interactions of the gnens could increase invasion and metastasis dangers of the colon cancer.
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Project Supported:
Project supported by the Science Research Foundation from Bureau of Education of Henan Province (No.2011A320015)
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