代谢标志物己糖激酶1（HK1）和丙酮酸激酶M2（PKM2）的过表达促进中国胃癌的淋巴转移和不良预后。
Overexpression of metabolic markers HK1 and PKM2 contributes to lymphatic metastasis and adverse prognosis in Chinese gastric cancer.
作者信息
Gao Yunshu, Xu Dongyun, Yu Guanzhen, Liang Jun
机构信息
Department of Oncology, The Affiliated Hospital of Qingdao University Qingdao 266000, Shandong, China ; Department of Oncology, 401 Hospital of PLA Qingdao 266000, Shandong, China.
Department of Oncology, No. 97 Hospital of PLA Xuzhou 221003, Jiangsu, China.
出版信息
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9264-71. eCollection 2015.
Abstract
Hexokinase 1 (HK1) and pyruvate kinase M2 (PKM2) are two key regulators in glycosis and oncogenic markers in cancers. In the present study, we investigated the expression profile by Western blotting and immunohistochemistry and determined their prognostic values in the gastric cancer. Expression of HK1 and PKM2 was remarkably increased in gastric cancer tissues and was significantly associated lymphatic metastasis and advanced TNM staging. In the COX regression model, HK1 and TNM stage were analyzed as adverse prognostic indicators in gastric cancer. Furthermore, patients with HK1 expression showed remarkable shorter survival duration in both lymphatic metastasis cohort and advanced staging cohort. Our results suggest that overexpression of PKM2 and HK1, especially the latter, significantly associates with lymphatic metastasis, advanced clinical staging and unfavorable prognosis in gastric cancer.
摘要
己糖激酶1（HK1）和丙酮酸激酶M2（PKM2）是糖酵解过程中的两个关键调节因子，也是癌症中的致癌标志物。在本研究中，我们通过蛋白质免疫印迹法和免疫组织化学研究了它们的表达谱，并确定了它们在胃癌中的预后价值。HK1和PKM2在胃癌组织中的表达显著增加，且与淋巴转移和TNM分期进展显著相关。在COX回归模型中，HK1和TNM分期被分析为胃癌的不良预后指标。此外，在淋巴转移队列和晚期分期队列中，HK1表达阳性的患者生存时间显著缩短。我们的结果表明，PKM2和HK1的过表达，尤其是后者，与胃癌的淋巴转移、临床分期进展及不良预后显著相关。
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本文引用的文献
1
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Br J Cancer. 2014 Oct 28;111(9):1757-64. doi: 10.1038/bjc.2014.492. Epub 2014 Sep 18.
2
PKM2: the thread linking energy metabolism reprogramming with epigenetics in cancer.丙酮酸激酶M2：连接癌症中能量代谢重编程与表观遗传学的纽带
Int J Mol Sci. 2014 Jun 26;15(7):11435-45. doi: 10.3390/ijms150711435.
3
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Cancer Invest. 2014 Aug;32(7):330-8. doi: 10.3109/07357907.2014.919306. Epub 2014 Jun 2.
4
PKM2 contributes to cancer metabolism.PKM2 促进癌症代谢。
Cancer Lett. 2015 Jan 28;356(2 Pt A):184-91. doi: 10.1016/j.canlet.2014.01.031. Epub 2014 Feb 4.
5
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Cell Signal. 2013 Dec;25(12):2685-92. doi: 10.1016/j.cellsig.2013.08.035. Epub 2013 Sep 7.
6
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Cancer Cell. 2013 Aug 12;24(2):213-228. doi: 10.1016/j.ccr.2013.06.014. Epub 2013 Aug 1.
7
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8
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10
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