M2型丙酮酸激酶在肝内胆管细胞癌组织中的表达及临床意义

Expression and Clinical Significance of Pyruvate Kinase M2 in Intrahepatic Cholangiocarcinoma

【目的】探讨M2型丙酮酸激酶(PKM2)在肝内胆管细胞癌(ICC)组织中表达以及临床意义。【方法】对中山大学附属第一医院2008年1月至2010年9月期间行手术治疗的86例ICC患者的癌组织及癌旁组织运用免疫组化方法检测PKM2的表达水平,统计学分析PKM2的表达与ICC患者临床病理特征之间的关系,并作生存分析及预后因素评估。【结果】ICC组织中PKM2的表达明显高于癌旁组织(P<0.001)。癌组织中淋巴结转移患者中PKM2的表达明显高于非淋巴结转移患者(P<0.001);无远处转移患者中PKM2的表达明显低于远处转移者(P=0.002);发生低分化肿瘤的PKM2的表达明显高于中、高分化肿瘤(P=0.048);临床分期Ⅳ期的患者中PKM2表达明显高于Ⅰ、Ⅱ、Ⅲ期患者(P=0.006);肿瘤有神经束侵犯的患者PKM2表达明显高于无神经束侵犯患者(P=0.024)。生存分析提示ICC患者中PKM2高表达组的5年生存率(0%)明显低于PKM2低表达组(15%),差异具有统计学意义(P<0.001)。单因素和多因素分析均表明PKM2的表达(P<0.001)和神经束侵犯(P=0.012)为ICC患者的不良预后因素。【结论】PKM2与ICC的恶性特征密切相关,PKM2为ICC患者不良预后的独立因素。

[ Objectives] To investigate the expression and clinical significance of pyruvate kinase M2 （PKM2） in intrahepatic cholangiocarcinoma （ICC）. [Methods] A total of 86 ICC patients who underwent surgical treatment between January 2008 and September 2010 were involved in this study. The expression of PKM2 in 86 pairs of ICC tissues and adjacent non-carcinomous tissues was detected by immunohistochemistry. Then the correlation between the expression of PKM2 and the clinicopathological characteristics of ICC patients was analyzed by statistical methods. Kaplan-Meier survival analysis was performed to evaluate the prognostic factors in ICC patients. [ Results] The expression of PKM2 in ICC tissues was significantly higher than that in adjacent non- carcinomous tissues （P 〈 0.001）. PKM2 levels were significantly higher in ICC cases with lymphatic metastasis than that without lymphatic metastasis （P 〈 0.001）, likewise in poorly differentiated adenocarcinomas than that in well and moderately differentiated adenocarcinomas （P = 0.048）. PKM2 expression in ICC patients without distant metastasis was significantly lower than that in patients with distant metastasis （P = 0.002）. PKM2 expression in ICC patients with clinical stage 1V was significantly higher than that in the patients with clinical stage I , lI and I1[ （P = 0.006）. PKM2 levels were also significantly higher in ICC cases with perineural invasion than that without perineural invasion （P = 0.024）. The 5-years overaU survival rate in high PKM2 expression group （0%） was significantly lower than that in low PKM2 expression group （15%） of ICC patients （P 〈 0.001）. Univariate and multivariate analysis demonstrated that PKM2 expression （P 〈 0.001） and perineural invasion （P = 0.012） were adverse significant prognostic factors for ICC patients. [ Conclusions ] PKM2 high expression was associated with malignant characteristics of ICC. PKM2 could be used as an independent prognostic factor for ICC patients.