<trans-title xml:lang="en"/>_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

¹ ,  ²

1. ;
2. ;

Corresponding author：

, Email: zhengjuc@126.com

Keywords：

M2型丙酮酸激酶; 肝细胞癌; Warburg效应

DOI：

10.7507/1007-9424.201606005

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目的探讨 M2 型丙酮酸激酶（PKM2）在肝细胞癌（以下简称“肝癌”）组织中的表达，并分析其与肝癌患者临床病理特征及预后的关系。方法收集 2008 年 1 月至 2011 年 1 月期间重庆市第九人民医院和重庆市九龙坡第二人民医院病理诊断为肝癌的石蜡标本，采用免疫组织化学方法检测肝癌组织中 PKM2 蛋白的表达，采用Kaplan-Meier 生存分析法、Cox 回归法分析 PKM2 蛋白表达与肝癌患者临床预后的关系。结果共收集 196 例肝癌患者的石蜡组织标本，其中 129 例（65.8%）肝癌患者的肝癌组织中 PKM2 蛋白高表达，其高表达与肝癌患者的性别（P=0.049鴐、肿瘤分化程度（P=0.000鴐、血清甲胎蛋白水平（P=0.010鴐、肿瘤数目（P=0.002）及 TNM 分期（P=0.001）有关，而与患者的年龄、有无肝硬化、肿瘤最大直径及乙肝表面抗原无关（P>0.05鴐。PKM2 蛋白高表达患者的 1、3、5 年总体生存率和无瘤生存率均明显低于 PKM2 低表达患者（P<0.05鴐，且多因素 Cox 回归分析结果显示 PKM2 蛋白高表达是肝癌患者总体生存率（HR=1.661，P=0.024）及无瘤生存率（HR=1.662，P=0.013）的独立危险因素。结论 PKM2 可能对肝癌患者的生物学行为有重要影响，可作为判断肝癌预后的一个新指标。

Citation： 何中林, 成正军. . CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(2): 248-251. doi: 10.7507/1007-9424.201606005 Copy

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2.	Devic S. Warburg effect—a consequence or the cause of carcinogenesis? J Cancer, 2016, 7(7): 817-822.
3.	Warburg O. On the origin of cancer cells. Science, 1956, 123(3191): 309-314.
4.	Fan FT, Shen CS, Tao L,et al. PKM2 regulates hepatocellular carcinoma cell epithelial-mesenchymal transition and migration upon EGFR activation. Asian Pac J Cancer Prev, 2014, 15(5): 1961-1970.
5.	Bhardwaj A, Das S. SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions. Proc Natl Acad Sci USA, 2016, 113(5): E538-E547.
6.	Iansante V, Choy PM, Fung SW,et al. PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation. Nat Commun, 2015, 6: 7882.
7.	Zhang X, He C, He C,et al. Nuclear PKM2 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma. Pathol Res Pract, 2013, 209(8): 510-515.
8.	Zhan C, Shi Y, Lu C,et al. Pyruvate kinase M2 is highly correlated with the differentiation and the prognosis of esophageal squamous cell cancer. Dis Esophagus, 2013, 26(7): 746-753.
9.	Teng Y, Ai Z, Wang Y,et al. Proteomic identification of PKM2 and HSPA5 as potential biomarkers for predicting high-risk endometrial carcinoma. J Obstet Gynaecol Res, 2013, 39(1): 317-325.
10.	郭枫, 陈韵. PKM2 蛋白在胃癌组织中的表达及其预后价值. 临床肿瘤学杂志, 2014, 19(7): 599-602.
11.	Kitamura K, Hatano E, Higashi T,et al. Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis. J Hepatol, 2011, 55(4): 846-857.
12.	Dong T, Yan Y, Chai H,et al. Pyruvate kinase M2 affects liver cancer cell behavior through up-regulation of HIF-1α and Bcl-xL in culture. Biomed Pharmacother, 2015, 69: 277-284.
13.	Liu WR, Tian MX, Yang LX,et al. PKM2 promotes metastasis by recruiting myeloid-derived suppressor cells and indicates poor prognosis for hepatocellular carcinoma. Oncotarget, 2015, 6(2): 846-861.
14.	Hu W, Lu SX, Li M,et al. Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma. Oncotarget, 2015, 6(9): 6570-6583.
15.	Chen Z, Lu X, Wang Z,et al. Co-expression of PKM2 and TRIM35 predicts survival and recurrence in hepatocellular carcinoma. Oncotarget, 2015, 6(4): 2538-2548.

1. Yang J, Wang C, Zhao F,et al. Loss of FBP1 facilitates aggressive features of hepatocellular carcinoma cells through the Warburg effect. Carcinogenesis, 2016 Oct 14. pii: bgw109.
2. Devic S. Warburg effect—a consequence or the cause of carcinogenesis? J Cancer, 2016, 7(7): 817-822.
3. Warburg O. On the origin of cancer cells. Science, 1956, 123(3191): 309-314.
4. Fan FT, Shen CS, Tao L,et al. PKM2 regulates hepatocellular carcinoma cell epithelial-mesenchymal transition and migration upon EGFR activation. Asian Pac J Cancer Prev, 2014, 15(5): 1961-1970.
5. Bhardwaj A, Das S. SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions. Proc Natl Acad Sci USA, 2016, 113(5): E538-E547.
6. Iansante V, Choy PM, Fung SW,et al. PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation. Nat Commun, 2015, 6: 7882.
7. Zhang X, He C, He C,et al. Nuclear PKM2 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma. Pathol Res Pract, 2013, 209(8): 510-515.
8. Zhan C, Shi Y, Lu C,et al. Pyruvate kinase M2 is highly correlated with the differentiation and the prognosis of esophageal squamous cell cancer. Dis Esophagus, 2013, 26(7): 746-753.
9. Teng Y, Ai Z, Wang Y,et al. Proteomic identification of PKM2 and HSPA5 as potential biomarkers for predicting high-risk endometrial carcinoma. J Obstet Gynaecol Res, 2013, 39(1): 317-325.
10. 郭枫, 陈韵. PKM2 蛋白在胃癌组织中的表达及其预后价值. 临床肿瘤学杂志, 2014, 19(7): 599-602.
11. Kitamura K, Hatano E, Higashi T,et al. Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis. J Hepatol, 2011, 55(4): 846-857.
12. Dong T, Yan Y, Chai H,et al. Pyruvate kinase M2 affects liver cancer cell behavior through up-regulation of HIF-1α and Bcl-xL in culture. Biomed Pharmacother, 2015, 69: 277-284.
13. Liu WR, Tian MX, Yang LX,et al. PKM2 promotes metastasis by recruiting myeloid-derived suppressor cells and indicates poor prognosis for hepatocellular carcinoma. Oncotarget, 2015, 6(2): 846-861.
14. Hu W, Lu SX, Li M,et al. Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma. Oncotarget, 2015, 6(9): 6570-6583.
15. Chen Z, Lu X, Wang Z,et al. Co-expression of PKM2 and TRIM35 predicts survival and recurrence in hepatocellular carcinoma. Oncotarget, 2015, 6(4): 2538-2548.

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