磷酸化MEK2(Thr394)在结直肠癌中的表达及其临床意义

Expression of phosphorylated MEK2 (Thr394) in colorectal cancer and its clinical implication

目的:探讨MAPK信号转导途径中MEK2蛋白第394号位点苏氨酸残基(Thr394)磷酸化在结直肠癌发病机制中的作用及临床意义。方法:采用组织芯片和免疫组织化学方法检测96例结直肠癌组织、24例结直肠腺瘤组织和24例癌旁正常组织的p-MEK2(Thr394)蛋白表达并比较其表达差异;此外,对前面的96例以及另外的337例临床病例参数和预后资料完善的结直肠癌患者,采用组织芯片-免疫组织化学方法检测p-MEK2(Thr394)的表达,并分析其与结直肠癌的预后及临床病例参数的相关性。结果:p-MEK2(Thr394)在癌旁正常组织、结直肠腺瘤和结直肠癌组织中表达呈递减趋势,其高表达率分别为100%、66.7%、19.8%,差异有统计学意义(P<0.01)。p-MEK2(Thr394)蛋白的表达与性别、年龄、体重指数、分化程度、T分期、N分期、TNM分期、肝转移及K-ras基因突变情况等临床病理参数间均无显著相关性(P>0.05)。Kaplan-Meier分析显示,p-MEK2(Thr394)表达与结直肠癌患者预后无显著相关性。结论:MEK2蛋白第394号位点上的苏氨酸残基磷酸化在癌旁正常组织和结直肠腺瘤、结直肠癌组织中的表达呈下降趋势,提示其可能与结直肠癌的发生及发展相关。

AIM ： To analyze the phosphorylation of Thr394 residue of mitogen extracellular kinase 2 （MEK2） protein in human colorectal tissues and its clinical significance. METHODS： Formalin-fixed, paraffin-embedded human colorectal tissue specimens were immunostained with the antibody against p-MEK2 （Thr394）. The expression levels of pMEK2 in normal mucosa （n =24）, adenoma （n =24） and adenocarcinoma （n =96） of colorectum were compared. Another group of colorectal adenocarcinoma samples （n = 417） was used to analyze the expression of p-MEK2 （Thr394） and its relationship with clinicopathological parameters and overall survival. RESULTS： The expression level of p-MEK2 （Thr394） in normal mucosa was 100%, in colorectal adenomas was 66.7% and in coloreetal adenocarcinoma was 19. 8%, showing the tendency of decrement and statistically significant differences. No significant correlation between the expression level of p-MEK2 （Thr394） and the clinieopathological parameters including sex, age, body mass index, differentiation degree, T stage, N stage, TNM stage, hepatic metastasis and mutation of K-ras was observed. Moreover, KaplanMeier analysis showed that the expression level of p-MEK2 （Thr394） and the orogrnosis of colorectal cancer had no signifi-cant correlation. CONCLUSION ： Reduction of p-MEK2 （Thr394） expression occurs during colorectal tumorigenesis. The phosphorylation of Thr394 residue in MEK2 may play an important role in the development of colorectal cancer.