Expression and gene polymorphisms of the chemokine CXCL5 in colorectal cancer patients.

Expression and gene polymorphisms of the chemokine CXCL5 in colorectal cancer patients.
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趋化因子CXCL5在结直肠癌患者中的表达及基因多态性

DOI:
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发表时间:
2007
影响因子:
5.2
通讯作者:
D. Wågsäter
D. Wågsäter
中科院分区:
医学2区
文献类型:
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作者:
J. Dimberg;O. Dienus;S. Löfgren;A. Hugander;D. Wågsäter

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一些研究表明,趋化因子在结直肠粘膜免疫中发挥重要作用,通过招募白细胞进出上皮附近的固有层。趋化因子CXCL 5是由结肠直肠粘膜内的上皮细胞表达的,是嗜中性粒细胞的化学引诱物,并且与克罗恩病和溃疡性结肠炎有关。此外,CXCL 5是一种促进与癌症相关的血管生成的趋化因子。本研究的目的是通过ELISA测定来确定与配对的正常粘膜相比,结肠直肠癌(CRC)组织(n=80)中CXCL 5蛋白水平是否改变。此外,还检查了来自CRC患者(n=62)与对照(n=71)相比的血浆CXCL 5水平。使用TaqMan系统,我们在CRC患者(n=228)和对照组(n=231)中筛选了-156G-> C和+398G->A CXCL 5基因变体,以评估CXCL 5基因型在CRC中的作用。分析显示,与对照组相比,结直肠肿瘤中的CXCL 5蛋白水平显著(P<0.0001)高于正常组织,而CRC患者的血浆中的CXCL 5蛋白水平较低(P=0.026)。免疫组化显示CXCL 5主要在大肠癌上皮细胞和正常上皮细胞中表达。此外,与正常组织中的-156G携带者相比,-156C携带者的患者具有更高的CXCL 5蛋白浓度(P=0.027),并且癌组织中的CXCL 5蛋白水平倾向于对于患者-156C携带者更高(P=0.059)。据我们所知,这是第一份关于CXCL 5基因变异的影响及其与人CRC中CXCL 5蛋白表达的关系的报告。
Several studies indicate that chemokines play important roles in colorectal mucosal immunity by recruiting leukocytes into and out of the lamina propria adjacent to the epithelium. The chemokine CXCL5 which is expressed by epithelial cells within colorectal mucosa is a chemoattractant for neutrophils and has been implicated in Crohn's disease and ulcerative colitis. In addition, CXCL5 is one chemokine which promote angiogenesis related to cancer. The objective of this study was to determine by ELISA assay whether CXCL5 protein level is altered in colorectal cancer (CRC) tissues (n=80) compared with paired normal mucosa. Furthermore, the plasma CXCL5 levels from CRC patients (n=62) compared with controls (n=71) were also examined. Using a TaqMan system we screened for -156G--> C and +398G-->A CXCL5 gene variants in CRC patients (n=228) and a control group (n=231) to assess the role of CXCL5 genotype in CRC. The analyses showed that CXCL5 protein level in colorectal tumours was significantly (P<0.0001) higher than in normal tissue and was lower in plasma in CRC patients compared with controls (P=0.026). Immunohistochemistry revealed CXCL5 immunoreactivity mainly in epithelial cells of the colorectal carcinoma and in normal epithelial cells. Furthermore, patients who were -156C carriers had higher CXCL5 protein concentration compared with -156G carriers in normal tissue (P=0.027) and CXCL5 protein levels in cancerous tissue tended to be higher for the patient -156C carriers (P=0.059). To our knowledge this is the first report on the influence of CXCL5 gene variants and their relation to expression of CXCL5 protein in human CRC.