Tumor Type M2 Pyruvate Kinase Expression in Gastric Cancer, Colorectal Cancer and Controls

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2004 May 27

PMID 15162541

Citations 25

Authors

Bo Zhang

Jian-Ying Chen

Dao-da Chen

Guo-Bin Wang

Ping Shen

Affiliations

Soon will be listed here.

Abstract

Aim: Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolytic flux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M(2). The present study was designed to evaluate the use of a new tumor marker, tumor M(2)-PK, in discriminating gastrointestinal cancer patients from healthy controls, and to compare with the reference tumor markers CEA and CA72-4.

Methods: The concentration of tumor M(2)-PK in body fluids could be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit (ScheBo Tech, Giessen, Germany). By using this kit, the tumor M(2)-PK concentration was measured in EDTA-plasma of 108 patients. For the healthy blood donors a cut-off value of 15 U/mL was evaluated, which corresponded to 90% specificity. Overall 108 patients were included in this study, 54 patients had a histological confirmed gastric cancer, 54 patients colorectal cancer, and 20 healthy volunteers served as controls.

Results: The cut-off value to discriminate patients from controls was established at 15 U/mL for tumor M(2)-PK. The mean tumor M(2)-PK concentration of gastric cancer was 26.937 U/mL. According to the TNM stage system, the mean tumor M(2)-PK concentration of stage I was 16.324 U/mL, of stage II 15.290 U/mL, of stage III 30.289 U/mL, of stage IV 127.31 U/mL, of non-metastasis 12.854 U/mL and of metastasis 35.711 U/mL. The mean Tumor M(2)-PK concentration of colorectal cancer was 30.588 U/mL. According to the Dukes stage system, the mean tumor M(2)-PK concentration of Dukes A was 16.638 U/mL, of Dukes B 22.070 U/mL, and of Dukes C 48.024 U/ml, of non-metastasis 19.501 U/mL, of metastasis 49.437 U/mL. The mean tumor M(2)-PK concentration allowed a significant discrimination of colorectal cancers (30.588 U/mL) from controls (10.965 U/mL) (P<0.01), and gastric cancer (26.937 U/mL) from controls (10.965 U/mL) (P<0.05). The overall sensitivity of tumor M(2)-PK for colorectal cancer was 68.52%, while that of CEA was 43.12%. In gastric cancer, tumor M(2)-PK showed a high sensitivity of 50.47%, while CA72-4 showed a sensitivity of 35.37%.

Conclusion: Tumor M(2)-PK has a higher sensitivity than markers CEA and CA72-4, and is a valuable tumor marker for the detection of gastrointestinal cancer.

Citing Articles

Evaluation of serum and pleural levels tumor M2-pyruvate kinase in lung cancer patients with pleural effusion.

Zhang T, Liu W, Li L, Jue Z, Xu C BMC Pulm Med. 2022; 22(1):307.

PMID: 35948914 PMC: 9364574. DOI: 10.1186/s12890-022-02103-x.

Biomarkers for Gastric Cancer Screening and Early Diagnosis.

Herrera-Pariente C, Montori S, Llach J, Bofill A, Albeniz E, Moreira L Biomedicines. 2021; 9(10).

PMID: 34680565 PMC: 8533304. DOI: 10.3390/biomedicines9101448.

Molecular and Metabolic Reprogramming: Pulling the Strings Toward Tumor Metastasis.

Hipolito A, Martins F, Mendes C, Lopes-Coelho F, Serpa J Front Oncol. 2021; 11:656851.

PMID: 34150624 PMC: 8209414. DOI: 10.3389/fonc.2021.656851.

Efficacy and mechanism of combination of oxaliplatin with PKM2 knockdown in colorectal cancer.

Yin C, Lu W, Ma M, Yang Q, He W, Hu Y Oncol Lett. 2020; 20(6):312.

PMID: 33093921 PMC: 7573921. DOI: 10.3892/ol.2020.12175.

Nonalcoholic fatty liver disease and gastric bypass surgery regulate serum and hepatic levels of pyruvate kinase isoenzyme M2.

Meoli L, Gupta N, Saeidi N, Panciotti C, Biddinger S, Corey K Am J Physiol Endocrinol Metab. 2018; 315(4):E613-E621.

PMID: 29462566 PMC: 6230703. DOI: 10.1152/ajpendo.00296.2017.

References

Hugo F, Fischer G, Eigenbrodt E . Quantitative detection of tumor M2-PK in serum and plasma. Anticancer Res. 1999; 19(4A):2753-7. View

Oremek G, Gerstmeier F, Sauer-Eppel H, Sapoutzis N, Wechsel H . Pre-analytical problems in the measurement of tumor type pyruvate kinase (tumor M2-PK). Anticancer Res. 2003; 23(2A):1127-30. View

Hoopmann M, Warm M, Mallmann P, Thomas A, Gohring U, Schondorf T . Tumor M2 pyruvate kinase--determination in breast cancer patients receiving trastuzumab therapy. Cancer Lett. 2002; 187(1-2):223-8. DOI: 10.1016/s0304-3835(02)00404-4. View

Schneider J, Neu K, Velcovsky H, Morr H, Eigenbrodt E . Tumor M2-pyruvate kinase in the follow-up of inoperable lung cancer patients: a pilot study. Cancer Lett. 2003; 193(1):91-8. DOI: 10.1016/s0304-3835(02)00720-6. View

Oremek G, Teigelkamp S, Kramer W, Eigenbrodt E, Usadel K . The pyruvate kinase isoenzyme tumor M2 (Tu M2-PK) as a tumor marker for renal carcinoma. Anticancer Res. 1999; 19(4A):2599-601. View

Schulze G . The tumor marker tumor M2-PK: an application in the diagnosis of gastrointestinal cancer. Anticancer Res. 2001; 20(6D):4961-4. View

Oremek G, Rutner F, Sapoutzis N, Sauer-Eppel H . Tumor marker pyruvate kinase type tumor M2 in patients suffering from diabetic nephropathy. Anticancer Res. 2003; 23(2A):1155-8. View

Mazurek S, Eigenbrodt E . The tumor metabolome. Anticancer Res. 2003; 23(2A):1149-54. View

Mazurek S, Grimm H, Boschek C, Vaupel P, Eigenbrodt E . Pyruvate kinase type M2: a crossroad in the tumor metabolome. Br J Nutr. 2002; 87 Suppl 1:S23-9. View

10.

Roigas J, Schulze G, Raytarowski S, Jung K, Schnorr D, Loening S . Tumor M2 pyruvate kinase in plasma of patients with urological tumors. Tumour Biol. 2001; 22(5):282-5. DOI: 10.1159/000050628. View

11.

Hardt P, Ngoumou B, Rupp J, Kloer H . Tumor M2-pyruvate kinase: a promising tumor marker in the diagnosis of gastro-intestinal cancer. Anticancer Res. 2001; 20(6D):4965-8. View

12.

Oremek G, Sapoutzis N, Kramer W, Bickeboller R, Jonas D . Value of tumor M2 (Tu M2-PK) in patients with renal carcinoma. Anticancer Res. 2001; 20(6D):5095-8. View

13.

Hardt P, Toepler M, Ngoumou B, Rupp J, Kloer H . Measurement of fecal pyruvate kinase type M2 (tumor M2-PK) concentrations in patients with gastric cancer, colorectal cancer, colorectal adenomas and controls. Anticancer Res. 2003; 23(2A):851-3. View

14.

Wechsel H, Petri E, Bichler K, Feil G . Marker for renal cell carcinoma (RCC): the dimeric form of pyruvate kinase type M2 (Tu M2-PK). Anticancer Res. 1999; 19(4A):2583-90. View

15.

Schneider J, Morr H, Velcovsky H, Weisse G, Eigenbrodt E . Quantitative detection of tumor M2-pyruvate kinase in plasma of patients with lung cancer in comparison to other lung diseases. Cancer Detect Prev. 2001; 24(6):531-5. View

16.

Pezzilli R, Migliori M, Morselli-Labate A, Campana D, Ventrucci M, Tomassetti P . Diagnostic value of tumor M2-pyruvate kinase in neuroendocrine tumors. A comparative study with chromogranin A. Anticancer Res. 2003; 23(3C):2969-72. View

17.

Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E, Jansen-Durr P . Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci U S A. 1999; 96(4):1291-6. PMC: 15456. DOI: 10.1073/pnas.96.4.1291. View

18.

Roigas J, Schulze G, Raytarowski S, Jung K, Schnorr D, Loening S . [Tumor M2 pyruvate kinase in renal cell carcinoma. Studies of plasma in patients]. Urologe A. 2001; 39(6):554-6. DOI: 10.1007/s001200050410. View

19.

Aisaki K, Kanno H, Oyaizu N, Hara Y, Miwa S, Ikawa Y . Apoptotic changes precede mitochondrial dysfunction in red cell-type pyruvate kinase mutant mouse erythroleukemia cell lines. Jpn J Cancer Res. 1999; 90(2):171-9. PMC: 5926040. DOI: 10.1111/j.1349-7006.1999.tb00730.x. View

20.

Schneider J, Neu K, Grimm H, Velcovsky H, Weisse G, Eigenbrodt E . Tumor M2-pyruvate kinase in lung cancer patients: immunohistochemical detection and disease monitoring. Anticancer Res. 2002; 22(1A):311-8. View