VHL、NFκB和CXCR4状态与结肠癌肝转移的关系

Correlation of CXCR4,VHL and NFκB Status with Colorectal Cancer Metastasis

[目的]探讨VHL基因突变、CXCR4表达和NFκB激活与结肠癌肝转移的关系。[方法]收集2005年3月～2007年12月Ⅱ～Ⅲ期结肠癌患者67例。分别通过聚合酶链反应—单链构象多态性分析VHL基因突变,RT-PCR检测CXCR4表达,凝胶电泳迁移实验检测NFκB活性,随访24个月。[结果]67例结肠癌患者中CXCR4 mRNA高表达为32.84%(22/67);VHL基因突变率为28.36%(19/67);NFκB激活比例为29.85%(20/67)。随访24个月,16例出现肝转移患者,13例出现其它部位的转移和38例无病情进展。16例出现肝转移患者中CXCR4 mRNA高表达、VHL基因突变和NFκB激活分别为15、11和13例,明显高于未出现转移的其他部位转移的患者和无病情进展患者(P<0.01)。[结论]VHL基因突变和CXCR4上调和NFκB激活可能参与结肠癌肝转移的发生。

[Purpose] To investigate the relation of VHL mutation, chemokine receptor （CXCR4） expression and NFkB activation with liver metastases in patients with colorectal cancer. [Methods ] Sixty seven cases with colorectal cancer stage Ⅱ～Ⅲ from Mar,2005 to Dec, 2007 were assessed and followed-up for 24 months. VHL mutation, CXCR4 expression and NFkB were validated by RT-PCR, SSP-PCR and electrophoretic mobility shift assays, respectively. [Results] In 67 cases with colorectal cancer, high expression rate with CXCR4 mRNA was 32.84%（22/67）, VHL mutation rate was 28.36%（19/67）, NFkB activation rate was 29.85%（20/67）. In 24 months followup, 16 patients developed metastases in the liver; 13, in other organs and 38, progression free. In liver metastases patients, a high CXCR4 expression, VHL mutation and NFKB activation were 15, 11 and 13 respectively, compared with non liver metastases and progression free patients（P〈0.01 ）. [Conclusionsl CXCR4 gene expression, VHL mutation and NFkB activation in patients with colorectal cancer might contribute to liver metastases.