c-Jun基因启动子区多态性位点rs4646999与肠癌预后的相关性  

Correlation between rs4646999 polymorphism of c-jun gene promoter and prognosis of colorectal cancer

作　　者：陈典克[1] 罗倩欣 俞希虎 甘肖勤[1] 林溢恒[1] 吴培煌[3] 王磊[2] 

机构地区：[1]中山大学附属第六医院肿瘤内科,510655 [2]中山大学附属第六医院结直肠外科,510655 [3]中山大学附属第六医院广东省结直肠盆底疾病研究重点实验室,510655

出　　处：《实用医学杂志》2017年第21期3518-3523,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金青年项目(编号:81201581);广东省自然科学基金面上项目(编号:S2013010013478);广州市科技计划项目(编号:201707010430)

摘　　要：目的探讨c-Jun基因启动子多态性位点rs4646999与肠癌预后的相关性。方法采用Taq-Man探针法检测436例肠癌患者rs4646999-673C>T的基因型,通过Kaplan-Meier法和Cox回归分析其生存曲线;采用免疫印迹分析多态性位点不同基因型的c-Jun蛋白表达水平。结果单因素分析表明携带TT基因型患者累积生存率显著高于CT和CC基因型携带者,差异有统计学意义。多因素Cox回归分析显示分化程度、淋巴结转移、远处转移、TNM分期和rs4646999位点基因型为预后因素,CT/CC基因型与肠癌较差的生存预后相关(P<0.05)。蛋白表达分析发现CC基因型癌组织c-Jun蛋白表达升高,而TT基因型则相反。结论 c-Jun基因启动子区域多态性位点rs4646999与肠癌生存预后相关,其作用机制可能是增强c-Jun蛋白表达导致肠癌发生发展。Objective To detect the association between rs4646999 polymorphisms in the promoter regionof the c-Jun and the prognosis of sporadic colorectal cancer. Methods rs4646999-673 C > T genetypes were deter-mined by Taqman-MGB probes in 436 colorectal cancer cases. The survival curve was analyzed by Kaplan-Meieranalysis and Cox regression. Western blot was used to analyze the expression levels of c-Jun protein in different gen-otypes. Results Univariate analysis showed that the cumulative survival rate of patients with rs4646999 TT geno-type was significantly higher than that of patients with CT and CC genotype. Multivariate Cox regression analysisshowed that the differentiation,lymph node metastasis,distant metastasis,TNM stage and rs4646999 genetypeswere prognostic factors. Compared with the carriers of TT genotype,CT/CC complex genotypes were associated withpoor prognosis of colorectal cancer(P < 0.05). Protein expression analysis showed that the expression of c-Jun pro-tein in CC genotype was increased. In contrast,the TT genotype was decreased. Conclusions This study providedthe evidence that rs4646999-673 C > T genetic variant in c-Jun promoter regions is associated with the poor survivalprognosis of colorectal cancer,possibly by elevating the protein expression levels that appeared to up-regulate activ-ity of c-Jun thus tumorigenesis.

关 键 词：结直肠癌 单核苷酸多态性 生存预后 C-JUN基因 

分 类 号：R735.3[医药卫生—肿瘤]