糖酵解关键酶在结直肠癌组织中的表达及其临床意义

Expression of glycolysis key enzymes in colorectal cancer tissues and its clinical significance

目的 :探讨糖酵解关键酶己糖激酶(hexokinase,HK)、磷酸果糖激酶(phosphofructokinase,PFK)和丙酮酸激酶M2(pyruvate kinase M2,PKM2)在结直肠癌组织中的表达及其临床意义。方法:应用免疫组织化学法检测结直肠癌组织及其相应癌旁组织中HK、PFK和PKM2的表达,并分析HK、PFK和PKM2的表达与结直肠癌患者临床病理特征间的关系,及其对患者预后的影响。应用MTT法、克隆形成和划痕愈合实验分别检测敲低HK、PFK和PKM2表达的结直肠癌HT29细胞的增殖、克隆形成及迁移能力。结果:结直肠癌组织中HK、PFK和PKM2的表达水平均显著高于其相应的癌旁组织(P值均<0.01)。HK的表达与结直肠癌患者的临床分期有关(P<0.01),PFK的表达与结直肠癌患者的肿瘤浸润深度和临床分期有关(P值均<0.01),PKM2的表达与肿瘤浸润深度、远处转移和临床分期有关(P值均<0.05)。HK及PKM2高表达的患者预后较差(P值均<0.05),HK、PFK和PKM2同时高表达的结直肠癌患者预后最差(P<0.05)。敲低HK、PFK和PKM2的表达后,HT29细胞的增殖(P值均<0.05)、克隆形成(P值均<0.01)及迁移能力(P值均<0.05)均下降。结论:糖酵解关键酶与结直肠癌的发生及进展密切相关,HK、PFK和PKM2同时高表达的结直肠癌患者预后较差。

Objective： To investigate the expressions of glycolysis key enzymes including hexokinase （HK）,phosphofructokinase （PFK） and pyruvate kinase M2（PKM2） in colorectal cancer tissues. Methods： The expressions of HK,PFK and PKM2 in colorectal cancer tissues and the para-carcinoma tissues were detected by immunohistochemistry,and the correlations of the expressions of HK,PFK and PKM2 with the clinicopathological features of the patients were analyzed.The effects of HK,PFK and PKM2 expressions on the prognosis were analyzed.The abilities of proliferation,colony formation and migration of HT29 cells with HK,PFK and PKM2 silencing were detected by MTT method,colony formation assay and wound healing assay,respectively. Results： The expression levels of HK,PFK and PKM2 in the colorectal cancer tissues were significantly higher than those in the para-carcinoma tissues （all P 〈 0.01）.The HK expression was significantly correlated with the clinical stage （P 〈 0.01）.The PFK expression was significantly correlated with the infiltration depth and the clinical stage （both P 〈 0.01）.The PKM2 expression was significantly correlated with the infiltration depth,distant metastasis and the clinical stage （all P 〈 0.05）.The prognosis of the patients with high expressions of HK and PKM2 was poor （P 〈 0.05）.The prognosis of the patients with high expressions of HK,PFK and PKM2 was poorest （P 〈 0.05）.The abilities of proliferation （P 〈 0.05）,colony formation （P 〈 0.01） and migration （P 〈 0.05） of the HT29 cells with HK,PFK and PKM2 silencing were inhibited. Conclusion： Glycolysis key enzymes are correlated with the occurrence and progression of the colorectal cancer.The prognosis of the colorectal cancer patients with high expressions of HK,PFK and PKM2 is poor.