BRAF基因突变对结肠癌伴随胃癌发生的影响

Effect of BRAF Gene Mutation on Colon Cancer and Associated With Gastric Cancer

目的研究BRAF基因突变与结肠癌伴随胃癌,以及PRDX1和PRDX6基因表达量的关联,分析PRDX1和PRDX6基因在结肠癌伴随其它原发癌症中的作用。方法收集47例患有结肠癌与伴随胃癌病人的样本,通过PNAClamp TM突变检测试剂盒检测样本中BRAF和MLH1基因的突变情况,利用卡方检验比较突变与相关特征的关系。通过q PCR和蛋白质印迹检测BRAF突变样本中的PRDX1和PRDX6的表达量变化。通过人类HCT-116结肠癌细胞中转入带有BRAF突变的质粒,研究细胞系水平BRAF突变对PRDX 1和PRDX 6表达量的影响。结果 BRAF的突变在不同年龄、癌症位置、多发癌时间间距、癌症数量或者家庭癌症史之间差异无显著性(P>0.05);而MLH1的突变在不同多发癌时间间距、癌症数量和家庭癌症史之间,差异有显著性(P<0.05)。PRDX1和PRDX6表达水平与BRAF突变程度及不同结肠癌伴随的原发癌数量之间差异有显著性(P<0.05),PRDX1和PRDX6基因可能是BRAF突变抑制的目标。结论结肠癌伴随胃癌的多种原发性癌症中BRAF突变率比较低。使用BRAF突变作为鉴定标记,仍需要其他基因如MLH1基因突变情况的辅助。BRAF突变可以抑制PRDX1和PRDX6基因的表达,而且PRDX1和PRDX6基因的表达量与结肠癌伴随的原发癌的数量有关。

Objective To investigate the association between BRAF mutation and colon cancer with stomach cancer, and between BRAF mutation and gene expression of PRDX6 and PRDX1, and to analyze the role of PRDX1 and PRDX6 gene in colon cancer with other primary cancers. Methods A total of 47 patients with colon cancer complicated by gastric cancer samples were collected. Mutation of BRAF and MLH1 genes were detected by PNAClampTM kit, and chi-square test was used to compare the relationship between mutations and related characteristics. Expressions of PRDX1 and PRDX6 were quantified by qPCR and Western blot in samples with and without BRAF mutation. The plasmid with the BRAF mutation was transferred into human HCT -116 colon cancer ceUs to investigate the expression levels of PRDX1 and PRDX6. Results BRAF mutation had no correlation with age, cancer location, multiple cancer time intervals and the number of cancer or fanfily history of cancer; while MLH1 mutation had correlation with cancer multiple time intervals and the number of cancer and family cancer history （P〈0.05）. PRDX1 and PRDX6 expression levels were correlated with the degree of the BRAF mutation and the number of primary cancer in colon cancer （P〈0.05）. PRDXI and PRDX6 might be the target of BRAF mutation inhibition. Conclusion BRAF mutation rate in colon cancer complicated by gastric cancer is relatively low in the Chinese population. When using BRAF mutation as a marker for detection, other genes such as MLH1 gene mutation may be as auxiliary. BRAF mutation inhibits PRDX1 and PRDX6, which in turn may affect the number of primary cancer.