DOI QR코드

DOI QR Code

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

  • Chang, Chih-Chun ;
  • Liou, Ching-Biau ;
  • Su, Ming-Jang ;
  • Lee, Yi-Chen ;
  • Liang, Chai-Ting ;
  • Ho, Jung-Li ;
  • Tsai, Huang-Wen ;
  • Yen, Tzung-Hai ;
  • Chu, Fang-Yeh
  • Published : 2015.10.06

Abstract

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

Keywords

Creatine kinase;cancer;tumor biomarker;CK-MB-to-total-CK ratio

References

  1. Balasubramani M, Day BW, Schoen RE, et al (2006). Altered expression and localization of creatine kinase B, heterogeneous nuclear ribonucleoprotein F, and high mobility group box 1 protein in the nuclear matrix associated with colon cancer. Cancer Res, 66, 763-9. https://doi.org/10.1158/0008-5472.CAN-05-3771
  2. Baldane S, Ipekci SH, Sozen M, et al (2015). Mean platelet volume could be a possible biomarker for papillary thyroid carcinomas. Asian Pac J Cancer Prev, 16, 2671-4. https://doi.org/10.7314/APJCP.2015.16.7.2671
  3. Chang CC, Chung YH, Liou CB, et al (2015). Influence of residential environment and lifestyle on multiple primary malignancies in Taiwan. Asian Pac J Cancer Prev, 16, 3533-8. https://doi.org/10.7314/APJCP.2015.16.8.3533
  4. Enooku K, Nakagawa H, Soroida Y, et al (2014). Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients. Int J Cancer, 135, 871-9. https://doi.org/10.1002/ijc.28720
  5. Gries A, Werle E, Wiesel M, et al (1997). False increased CK-MB value after cryoablation of the prostate without myocardial infarct. Anasthesiol Intensivmed Notfallmed Schmerzther, 32, 580-2. https://doi.org/10.1055/s-2007-995111
  6. Huddleston HG, Wong KK, Welch WR, et al (2005). Clinical applications of microarray technology: creatine kinase B is an up-regulated gene in epithelial ovarian cancer and shows promise as a serum marker. Gynecol Oncol, 96, 77-83. https://doi.org/10.1016/j.ygyno.2004.08.047
  7. Ishikawa J, Taniguchi T, Takeshita A, et al (2005). Increased creatine kinase BB activity and CKB mRNA expression in patients with hematologic disorders: relation to methylation status of the CKB promoter. Clin Chim Acta, 361, 135-40. https://doi.org/10.1016/j.cccn.2005.05.028
  8. Jap TS, Wu YC, Ho DM, et al (2000). Spuriously high CK-MB isoenzyme activity mimicking acute myocardial infarction in a patient with adenocarcinoma of the rectum. Zhonghua Yi Xue Za Zhi (Taipei), 63, 413-7.
  9. Joseph J, Cardesa A, Carreras J (1997). Creatine kinase activity and isoenzymes in lung, colon and liver carcinomas. Br J Cancer, 76, 600-5. https://doi.org/10.1038/bjc.1997.432
  10. Loo JM, Scherl A, Nguyen A, et al (2015). Extracellular metabolic energetics can promote cancer progression. Cell, 160, 393-406. https://doi.org/10.1016/j.cell.2014.12.018
  11. Meffert G, Gellerich FN, Margreiter R, et al (2005). Elevated creatine kinase activity in primary hepatocellular carcinoma. BMC Gastroenterol, 5, 9. https://doi.org/10.1186/1471-230X-5-9
  12. Mooney SM, Rajagopalan K, Williams BH, et al (2011). Creatine kinase brain overexpression protects colorectal cells from various metabolic and non-metabolic stresses. J Cell Biochem, 112, 1066-75. https://doi.org/10.1002/jcb.23020
  13. Qian XL, Li YQ, Gu F, et al (2012). Overexpression of ubiquitous mitochondrial creatine kinase (uMtCK) accelerates tumor growth by inhibiting apoptosis of breast cancer cells and is associated with a poor prognosis in breast cancer patients. Biochem Biophys Res Commun, 427, 60-6. https://doi.org/10.1016/j.bbrc.2012.08.147
  14. Ruiz Gines MA, Calafell Mas MF, Ruiz Gines JA, et al (2006). Macro creatine kinase: illness marker. Practical guide for the management. An Med Interna, 23, 272-5.
  15. Soroida Y, Ohkawa R, Nakagawa H, et al (2012). Increased activity of serum mitochondrial isoenzyme of creatine kinase in hepatocellular carcinoma patients predominantly with recurrence. J Hepatol, 57, 330-6. https://doi.org/10.1016/j.jhep.2012.03.012
  16. Tsai HW, Chang CC, Sun JT, et al (2014). Clinical features of patients with esophageal and second primary cancers. Asian Pac J Cancer Prev, 15, 9831-4. https://doi.org/10.7314/APJCP.2014.15.22.9831
  17. Uranbileg B, Enooku K, Soroida Y, et al (2014). High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential. Int J Cancer, 134, 2189-98 https://doi.org/10.1002/ijc.28547
  18. Vrbica Z, Durovic O, Oreb N (1997). Interference of CKBB isoenzyme in the determination of CK-MB using the immunoinhibition method in patients with pulmonary diseases. Lijec Vjesn, 119, 263-5.
  19. Wu AH, Bowers GN Jr (1982). Evaluation and comparison of immunoinhibition and immunoprecipitation methods for differentiating MB from BB and macro forms of creatine kinase isoenzymes in patients and healthy individuals. Clin Chem, 28, 2017-21.
  20. Z'Graggen WJ, Wehrli C, Gautschi K, et al (2000). Differential diagnostic considerations in CK-MB level increase. Praxis (Bern 1994), 89, 1864-7.
  21. Zarghami N, Giai M, Yu H, et al (1996). Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients. Br J Cancer, 73, 386-90. https://doi.org/10.1038/bjc.1996.66
  22. Zeng GQ, Zhang PF, Deng X, et al (2012). Identification of candidate biomarkers for early detection of human lung squamous cell cancer by quantitative proteomics. Mol Cell Proteomics, 11, 111.013946.