Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2018

Open Access 01-12-2018 | Research

Evaluation of tumor M2-pyruvate kinase (Tumor M2-PK) as a biomarker for pancreatic cancer

Authors: Indika A. Bandara, Minas Baltatzis, Sudip Sanyal, Ajith K. Siriwardena

Published in: World Journal of Surgical Oncology | Issue 1/2018

Login to get access

Abstract

Background

Expression of the dimeric M2 isoenzyme of pyruvate kinase, termed Tumor M2-PK, is increased in some human cancers. This study evaluates the potential role of pre-operative Tumor M2-PK as a marker of prognosis in patients with pancreatic malignancy.

Methods

Seventy-three consecutive patients with a clinical diagnosis of pancreatic or peri-ampullary cancer were enrolled. Their median (range) age was 66 (23–83) years. Pre-operative samples of venous blood were taken for analysis of Tumor M2-PK. The full study protocol was approved by the North West Research Ethics Committee (protocol number 06/MRE08/69).

Results

The mean (standard deviation) plasma Tumor M2-PK in pancreatic/peri-ampullary malignancy was 60.3 (106.5) U/ml and 22 U/ml (SD: 12 U/ml) in benign disease (p < 0.001). Multivariate Cox regression analysis showed that Tumor M2-PK (> 27 U/mL), Ca19-9 (> 39 U/ml), resection status, and disease stage were associated with poorer survival. Tumor M2-PK values greater than 27 U/ml were associated with inferior survival compared to those with lower values (hazard ratio 2.049, significantly increased risk of death, p = 0.042).

Conclusion

This preliminary study shows that an elevated level of Tumor M2-PK (with a cutoff threshold of 27 U/mL) measured pre-operatively is associated with poorer prognosis in patients with pancreatic and peri-ampullary cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Mazurek S, Grimm H, Oehmke Weisse G, Teigelkamp S, Eigenbrodt E. Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. Anticancer Res. 2000;20:5151–4.PubMed Mazurek S, Grimm H, Oehmke Weisse G, Teigelkamp S, Eigenbrodt E. Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. Anticancer Res. 2000;20:5151–4.PubMed
2.
go back to reference Wu J, Hu L, Chen M, Cao W, Chen H, He T. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies. Onco Targets Ther. 2016;9:4277–88.CrossRefPubMedPubMedCentral Wu J, Hu L, Chen M, Cao W, Chen H, He T. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies. Onco Targets Ther. 2016;9:4277–88.CrossRefPubMedPubMedCentral
3.
go back to reference Eigenbrodt E, Basenau D, Holthusen, Mazurek S, Fischer G. Quantification of tumor type M2 pyruvate kinase Tu M2-PK in human carcinomas. Anticancer Res. 1997;17:3153–6.PubMed Eigenbrodt E, Basenau D, Holthusen, Mazurek S, Fischer G. Quantification of tumor type M2 pyruvate kinase Tu M2-PK in human carcinomas. Anticancer Res. 1997;17:3153–6.PubMed
4.
go back to reference Hugo F, Fisher G, Eigenbrodt E. Quantitative detection of tumour M2-PK in serum and plasma. Anticancer Res. 1999;19:2753–7.PubMed Hugo F, Fisher G, Eigenbrodt E. Quantitative detection of tumour M2-PK in serum and plasma. Anticancer Res. 1999;19:2753–7.PubMed
5.
go back to reference Oremek GM, Eigenbrodt E, Radle J, Zeuzem S, Seiffert UB. Value of the serum levels of the tumour marker Tu M2-PK in pancreatic cancer. Anticancer Res. 1997;17:3031–4.PubMed Oremek GM, Eigenbrodt E, Radle J, Zeuzem S, Seiffert UB. Value of the serum levels of the tumour marker Tu M2-PK in pancreatic cancer. Anticancer Res. 1997;17:3031–4.PubMed
7.
go back to reference Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008;452:230–3.CrossRefPubMed Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008;452:230–3.CrossRefPubMed
8.
go back to reference Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol. 2011;43:969–80.CrossRefPubMed Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol. 2011;43:969–80.CrossRefPubMed
9.
go back to reference Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, et al. PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation. Mol Cancer. 2016;15:3.CrossRefPubMedPubMedCentral Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, et al. PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation. Mol Cancer. 2016;15:3.CrossRefPubMedPubMedCentral
10.
go back to reference Goonetilleke KS, Mason JM, Siriwardana P, King NK, France MW, Siriwardena AK. Diagnostic and prognostic value of tumor M2 pyruvate kinase in peri-ampullary cancer. Pancreas. 2007;34:318Y324.CrossRef Goonetilleke KS, Mason JM, Siriwardana P, King NK, France MW, Siriwardena AK. Diagnostic and prognostic value of tumor M2 pyruvate kinase in peri-ampullary cancer. Pancreas. 2007;34:318Y324.CrossRef
11.
go back to reference Kumar Y, Gurusamy K, Pamecha V, Davidson BR. Tumor M2-pyruvate kinase as tumor marker in exocrine pancreatic cancer a meta-analysis. Pancreas. 2007;35:114–9.CrossRefPubMed Kumar Y, Gurusamy K, Pamecha V, Davidson BR. Tumor M2-pyruvate kinase as tumor marker in exocrine pancreatic cancer a meta-analysis. Pancreas. 2007;35:114–9.CrossRefPubMed
12.
go back to reference Joergensen MT, Heegaard NH, Schaffalitzky de Muckadell OB. Comparison of plasma tumor M2-PK and CA19-9 in pancreatic cancer. Pancreas. 2010;39:243–7.CrossRefPubMed Joergensen MT, Heegaard NH, Schaffalitzky de Muckadell OB. Comparison of plasma tumor M2-PK and CA19-9 in pancreatic cancer. Pancreas. 2010;39:243–7.CrossRefPubMed
13.
go back to reference Mohammad GH, Olde Damink SW, Malago M, Dhar DK, Pereira SP. Pyruvate kinase M2 and lactate dehydrogenase a are overexpressed in pancreatic cancer and correlate with poor outcome. PLoS One. 2016;11:e0151635.CrossRefPubMedPubMedCentral Mohammad GH, Olde Damink SW, Malago M, Dhar DK, Pereira SP. Pyruvate kinase M2 and lactate dehydrogenase a are overexpressed in pancreatic cancer and correlate with poor outcome. PLoS One. 2016;11:e0151635.CrossRefPubMedPubMedCentral
14.
go back to reference Ogawa H, Nagano H, Konno M, Eguchi H, Koseki J, Kawamoto K, et al. The combination of the expression of hexokinase 2 and pyruvate kinase M2 is a prognostic marker in patients with pancreatic cancer. Mol Clin Oncol. 2015;3:563–71.CrossRefPubMedPubMedCentral Ogawa H, Nagano H, Konno M, Eguchi H, Koseki J, Kawamoto K, et al. The combination of the expression of hexokinase 2 and pyruvate kinase M2 is a prognostic marker in patients with pancreatic cancer. Mol Clin Oncol. 2015;3:563–71.CrossRefPubMedPubMedCentral
15.
go back to reference Durczynski A, Skulimowski A, Hogendorf P, Szymanski D, Kumor A et.al. The concentration of D-dimers in portal blood positively correlates with overall survival in patients with non-resectable pancreatic cancer. World J Surg Oncol. 2017;16;15(1):223. https://doi.org/10.1186/s12957-017-1291-4. Durczynski A, Skulimowski A, Hogendorf P, Szymanski D, Kumor A et.al. The concentration of D-dimers in portal blood positively correlates with overall survival in patients with non-resectable pancreatic cancer. World J Surg Oncol. 2017;16;15(1):223. https://​doi.​org/​10.​1186/​s12957-017-1291-4.
Metadata
Title
Evaluation of tumor M2-pyruvate kinase (Tumor M2-PK) as a biomarker for pancreatic cancer
Authors
Indika A. Bandara
Minas Baltatzis
Sudip Sanyal
Ajith K. Siriwardena
Publication date
01-12-2018
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2018
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-018-1360-3

Other articles of this Issue 1/2018

World Journal of Surgical Oncology 1/2018 Go to the issue