Expression of 6-phosphofructokinase-2 in colorectal cancer and its clinical significance

Lai Wei; Zhe Wang; Houjie Liang

doi:10.16016/j.1000-5404.201612084

您当前的位置：

首页 >

文章列表页 >

Expression of 6-phosphofructokinase-2 in colorectal cancer and its clinical significance

更新时间：2026-02-09

- Expression of 6-phosphofructokinase-2 in colorectal cancer and its clinical significance
- Journal of Third Military Medical University Vol. 39, Issue 10, Pages: 983-989(2017)
- 作者机构：
  
  400038 重庆，第三军医大学西南医院肿瘤科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81472698)
- DOI：10.16016/j.1000-5404.201612084
  CLC： R345.57;R730.23;R735.35
- Received：12 December 2016，
  
  Revised：2017-02-06，
  
  Published：30 May 2017
- 稿件说明：
移动端阅览
Lai Wei, Zhe Wang, Houjie Liang. Expression of 6-phosphofructokinase-2 in colorectal cancer and its clinical significance[J]. Journal of Third Military Medical University, 2017, 39(10): 983-989.
DOI：

Lai Wei, Zhe Wang, Houjie Liang. Expression of 6-phosphofructokinase-2 in colorectal cancer and its clinical significance[J]. Journal of Third Military Medical University, 2017, 39(10): 983-989. DOI： 10.16016/j.1000-5404.201612084.

摘要

目的

检测6-磷酸果糖-2-激酶(6-phosphofructokinase-2，PFKFB)在结直肠癌及癌旁组织中的表达，并探讨其临床意义。

方法

应用组织芯片结合免疫组化技术检测本院90例结直肠癌组织标本和相应90例癌旁组织中PFKFB1、PFKFB2、PFKFB3、PFKFB4及缺氧诱导因子-1(HIF1-α)的表达。

结果

PFKFB1、PFKFB2、PFKFB3、PFKFB4和HIF1-α在90例结直肠癌组织中高表达例数分别为57、59、59、51和60，表达均显著高于相应癌旁组织(

0.05)。PFKFB3在结直肠癌组织中的高表达与肿瘤的大小、临床分期、淋巴结转移及预后等密切相关(

0.05)，高表达组比低表达组预后差(

0.01)，临床分期高的结直肠癌患者中，PFKFB3的高表达提示了临床预后差(

0.01)，但在临床分期低的患者中不存在这种差异(

0.05)。PFKFB3的表达同HIF-1α的表达呈正相关(

=0.627

0.01)。而PFKFB1、PFKFB2和PFKFB4的表达与结直肠癌的肿瘤大小、临床分期、淋巴结转移及预后等无显著相关性(

0.05)。

结论

PFKFB家族在结直肠癌中高表达，且结直肠癌患者中PFKFB3高表达者比低表达者预后差，并且其作用同HIF1-α的表达密切相关。

Abstract

Objective

To investigate the expression level of 6-phosphofructokinase-2 (PFKFB) in human colorectal cancer and explore its clinical significance.

Methods

Tissue microarray combined with immunohistochemistry was used to detect the expression levels of PFKFB1

PFKFB2

PFKFB3

PFKFB4 and hypoxia-inducible factor-1(HIF1-α) in 90 colorectal cancer tissue samples and 90 paired adjacent tissue samples.

Results

High expression levels of PFKFB1

PFKFB2

PFKFB3

PFKFB4 and HIF1-α were detected in 57

51 and 60 of the colorectal cancer tissues

respectively

and their expression levels were significantly higher than in the paired adjacent tissues (

0.05). The expression level of PFKFB3 in the colorectal cancer tissue was closely correlated with the tumor size

clinical stage

lymph node metastasis and prognosis (

0.05). The patients with a high PFKFB3 expression level had poorer prognosis than those with a low PFKFB3 expression (

0.01). A high expression of PFKFB3 was

associated with a poor prognosis in the patients in an advanced stage (

0.01) but not in those in an early stage (

0.05). The expression level of PFKFB3 was positively correlated with HIF-1α (

=0.627

0.01). The expression levels of PFKFB1

PFKFB2 and PFKFB4 showed no obvious correlations with the tumor size

clinical stage

lymph node metastasis

or prognosis of the patients (

0.05).

Conclusion

The PFKFB family is highly expressed in colorectal cancers. A high expression of PFKFB3

which is positively correlated with HIF-1α expression

is associated with a poor prognosis of the patients

suggesting the potential role of PFKFB3 in tumorigenesis and progression of colorectal cancer.

关键词

Keywords

references

[American Cancer Society. Colorectal Cancer Facts & Figures 2011-2013[EB/OL ] . 2011, [2016-10-20 ] . http://www.cancer.org/acs/groups/content/epidemiologysurveilance/documents/document/acspc-028323.pdf. http://www.cancer.org/acs/groups/content/epidemiologysurveilance/documents/document/acspc-028323.pdf.

Tennant D A, Durán R V, Gottlieb E. Targeting metabolic transformation for cancer therapy[J]. Nat Rev Cancer, 2010, 10(4): 267-277. DOI:10.1038/nrc2817.

Cairns R A, Harris I S, Mak T W, et al. Regulation of cancer cell metabolism[J]. Nat Rev Cancer, 2011, 11(2): 85-95. DOI: 10.1038/nrc2981.

Gold J. Metabolic profiles in human solid tumors.I.A new technic for the utilization of human solid tumors in cancer research and its application to the anerobic glycolysis of isologous benign and malignant colon tissues[J]. Cancer Res, 1966, 26(4): 695-705.

Guo Y, Feng L, Zhou Y, et al.Systematic review with meta-analysis: HIF-1α attenuates liver ischemia-reperfusion injury[J]. Transplant Rev (Orlando), 2015, 29(3): 127-134. DOI: 10.1016/j.trre.2015.05.001.

Warmoes M O, Locasale J W.Heterogeneity of glycolysis in cancers and therapeutic opportunities[J]. Biochem Pharmacol, 2014, 92(1): 12-21. DOI: 10.1016/j.bcp.2014.07.019.

Semenza G L, Hypoxia-inducible factor 1 and cardiovascular disease[J]. Annu Rev Physiol, 2014, 76: 39-56. DOI: 10.1146/annurev-physiol-021113-170322.

Bloch K, Smith H, van Hamel Parsons V, et al.Metabolic Alterations During the Growth of Tumour Spheroids[J]. Cell Biochem Biophys, 2014, 68(3): 615-628. DOI: 10.1007/s12013-013-9757-7.

Chesney J, Mitchell R, Benigni F, et al.An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element:role in tumor cell glycolysis and the Warburg effect[J]. Proc Natl Acad Sci U S A, 1999, 96(6): 3047-3052. DOI: 10.1073/pnas.96.6.3047.

许良中, 杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志, 1996, 6(4): 229-231.

Xu L Z, Yang W T. Criteria for judging the results of immunohistochemistry[J]. Chin Oncol, 1996, 6(4): 229-231.

Yalcin A, Clem B F, Simmons A, et al.Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases[J]. J Biol Chem, 2009, 284(36): 24223-24232. DOI: 10.1074/jbc.M109.016816.

De Bock K, Georgiadou M, Schoors S, et al.Role of PFKFB3-driven glycolysis in vessel sprouting[J]. Cell, 2013, 154(3): 651-663. DOI: 10.1016/j.cell.2013.06.037.

Ji D, Lu Z T, Li Y Q, et al. MACC1 expression correlates with PFKFB2 and survival in hepatocellular carcinoma[J]. Asian Pac J Cancer Prev, 2014, 15(2): 999-1003. DOI: 10.7314/APJCP.2014.15.2.999.

Goidts V, Bageritz J, Puccio L, et al. RNAi screening in glioma stem-like cells identifies PFKFB4 as a key molecule important for cancer cell survival[J]. Oncogene, 2012, 31(27): 3235-3243. DOI: 10.1038/onc.2011.490.

Ros S, Santos C R, Moco S, et al. Functional metabolic screen identifies 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 4 as an important regulator of prostate cancer cell survival[J]. Cancer Discov, 2012, 2(4): 328-343. DOI: 10.1158/2159-8290.CD-11-0234.

Unwith S, Zhao H, Hennah L, et al.The potential role of HIF on tumour progression and dissemination[J]. Int J Cancer, 2015, 136(11): 2491-2503. DOI: 10.1002/ijc.28889.

Yalcin A, Clem B F, Imbert F Y, et al. 6-Phosphofructo-2-kinase (PFKFB3) promotes cell cycle progression and suppresses apoptosis via Cdk1-mediated phosphorylation of p27[J]. Cell Death Dis, 2014, 5: e1337. DOI: 10.1038/cddis.2014.292.

Warburg O, Wind F, Negelein E, et al. The metabolism of tumors in the body[J]. J Gen Physiol, 1927, 8(6): 519-530.

Dornbos D 3rd, Zwagerman N, Guo M, et al.Preischemic exercise reduces brain damage by ameliorating metabolic disorder in ischemia/reperfusion injury[J]. J Neurosci Res, 2013, 91(6): 818-827. DOI: 10.1002/jnr.23203.

Obach M, Navarro S A, Caro J, et al. 6-Phosphofructo-2-kinase (PFKFB3) gene promoter contains hypoxia-inducible factor-1 binding sites necessary for transactivation in response to hypoxia[J]. J Biol Chem, 2004, 279(51): 53562-53570. DOI: 10.1074/jbc.M406096200.

Novellasdemunt L, Bultot L, Manzano A, et al.PFKFB3 activation in cancer cells by the p38/MK2 pathway in response to stress stimuli[J]. Biochem J, 2013, 452(3): 531-543. DOI: 10.1042/BJ20121886.

Bando H, Atsumi T, Nishio T, et al.Phosphorylation of the 6-phosphofructo-2-kinase/fructose 2, 6-bisphosphatase/PFKFB3 family of glycolytic regulators in human cancer[J]. Clin Cancer Res, 2005, 11(16): 5784-5792. DOI: 10.1158/1078-0432.

Minchenko O, Opentanova I, Caro J. Hypoxic regulation of the 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase gene family (PFKFB-1-4) expression in vivo [J ] . FEBS Lett, 2003, 554(3): 264-270. DOI: 10.1016/S0014-5793(03)01179-7.

Doherty J R, Cleveland J L.Targeting lactate metabolism for cancer therapeutics[J]. J Clin Invest, 2013, 123(9): 3685-3692. DOI: 10.1172/JCI69741.

Granchi C, Minutolo F. Anticancer agents that counteract tumor glycolysis.[J]Chem Med Chem, 2012, 7(8): 1318-1350. DOI: 10.1002/cmdc.201200176.

Michael C C, Song G K, David N, et al.Molecular basis of the fructose-2, 6-bisphosphatase reaction of PFKFB3:Transition state and the C-terminal function[J].Proteins, 2012, 80(4): 1143-1153. DOI: 10.1002/prot.24015.

Bobarykina A Y, Minchenko D O, Opentanova I L, et al.Hypoxic regulation of PFKFB-3 and PFKFB-4 gene expression in gastric and pancreatic cancer cell lines and expression of PFKFB genes in gastric cancers[J]. Acta Biochim Pol, 2006, 53(4): 789-799.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Expression and clinical significance of 3β-hydor-xysteroid-△24 reducase in colorectal cancer

Expression of fatty acid amide hydrolase in colorectal cancer and its clinical significance

MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer

Efficacy and safety of immunotherapy combined with targeted therapy and chemotherapy in third-line treatment of microsatellite stable metastatic colorectal cancer

Preparation of nanosized hypoxia-inducible factor 1α inhibitor and its application in reversing chemoresistance in colorectal cancer cells

Related Author

王灿灿

王喆

秦虹

彭媛

张月

梁后杰

阮志华

邓佳

Related Institution

School of Medicine, Xinyang Hospital of Traditional Chinese Medicine

School of Pharmaceutical Sciences， Xinyang Vocational and Technical College， Xinyang， Henan, Xinyang Hospital of Traditional Chinese Medicine

Department of Pathology, Xinyang Hospital of Traditional Chinese Medicine

Department of Oncology, Renmin Hospital of Wuhan University

Department of Pharmacy, Renmin Hospital of Wuhan University

⁰