Skip to main content

Advertisement

Log in

Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Thymidine kinase 1 in serum (STK1) has been found to be a reliable proliferation marker in clinical trials. In this study, we examined the significance of STK1 in routine clinical settings.

Methods

The concentration of STK1 was determined by a sensitive dot blot ECL assay. The STK1 value was correlated to clinical stage and reactions and used for monitoring the outcome of surgery and/or multidrug chemotherapy of 1,247 patients with five different types of carcinomas (lung, esophagus, gastric, head and neck, and thyroid) in routine clinical settings.

Results

The STK1 values correlated with the clinical stage in patients with lung, esophagus, thyroid, and gastric carcinomas. After treatment, STK1 declined in all tumor groups after treatments (P < 0.01). The STK1 was low (<2 pM) or decreasing during treatment in patients with clinical reactions of complete response (CR) or partial response (PR), but high (>2 pM) or increasing in patients with stable disease (SD) or progressive disease (PD), some of them showing metastasis. STK1 also reflected the differences in clinical reactions when surgery and chemotherapy were compared.

Conclusion

We concluded that the concentration of TK1 in serum correlates to clinical stages and clinical reactions and monitors the effect of tumor therapies, not only in controlled clinical trials, but also in routine clinical settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Eissa S (1998) Tumor marker. Chapman & Hall, New York, pp 94–102, 134–137

  2. Tocchi A, Costa G, Lepre L et al (1998) The role of serum and gastric juice levels of carcinoembryonic antigen, CA19.9 and CA72.4 in patients with gastric cancer. J Cancer Res Clin Oncol 124:450–455

    Article  CAS  PubMed  Google Scholar 

  3. Ychou M, Duffour J, Kramer A et al (2000) Clinical significance and prognostic value of CA72-4 compared with CEA and CA19-9 in patients with gastric cancer. Dis Markers 16:105–110

    CAS  PubMed  Google Scholar 

  4. Dehaghani AS, Ghiam AF, Hosseini M et al (2007) Factors influencing serum concentration of CA125 and CA15-3 in iranian healthy postmenopausal women. Pathol Oncol Res 13:360–364

    Article  CAS  PubMed  Google Scholar 

  5. Pang RW, Joh JW, Johnson PJ et al (2008) Biology of hepatocellular carcinoma. Ann Surg Oncol 15:962–971

    Article  PubMed  Google Scholar 

  6. Ulmert D, Cronin AM, Bjork T et al (2008) Prostatic-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: a case-control study. BMC Med 6:6. doi:10.1186/1741-7015-6-6

    Article  PubMed  Google Scholar 

  7. Cheung KL, Evans AJ, Robertson JF (2001) The use of blood tumour markers in the monitoring of metastatic breast cancer unassessable for response to systemic therapy. Breast Cancer Res Treat 67:273–278

    Article  CAS  PubMed  Google Scholar 

  8. Hwa HL, Kuo WH, Chang LY et al (2008) Prediction of breast cancer and lymph node metastatic status with tumour markers using logistic regression models. J Eval Clin Pract 14:275–280

    Article  PubMed  Google Scholar 

  9. Locker GY, Hamilton S, Harris J et al (2006) ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 24:5313–5327

    Article  CAS  PubMed  Google Scholar 

  10. He Q, Skog S, Tribukait B (1991) Cell cycle related studies on thymidine kinase and its isoenzymes in Ehrlich ascites tumours. Cell Prolif 24:3–14

    Article  CAS  PubMed  Google Scholar 

  11. Kauffman MG, Kelly TJ (1991) Cell cycle regulation of thymidine kinase: residues near the carboxyl terminus are essential for the specific degradation of the enzyme at mitosis. Mol Cell Biol 11:2538–2546

    CAS  PubMed  Google Scholar 

  12. Ke PY, Chang ZF (2004) Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway. Mol Cell Biol 24:514–526

    Article  CAS  PubMed  Google Scholar 

  13. He Q, Wang N, Skog S et al (1996) Characterization of a peptide antibody against a C-terminal part of human and mouse cytosolic thymidine kinase, which is a marker for cell proliferation. Eur J Cell Biol 70:117–124

    CAS  PubMed  Google Scholar 

  14. Gronowitz JS, Hagberg H, Källander CF et al (1983) The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin’s lymphoma. Br J Cancer 47:487–495

    CAS  PubMed  Google Scholar 

  15. O’Neill KL, Abram WP, McKenna PG (1986) Serum thymidine kinase levels in cancer patients. Ir J Med Sci 155:272–274

    Article  PubMed  Google Scholar 

  16. Gronowitz JS, Bergström R, Nou E et al (1990) Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis. Cancer (Phila) 66:722–732

    Article  CAS  Google Scholar 

  17. Bresnick E, Mayfield ED Jr, Liebelt AG et al (1971) Enzyme patterns in a group of transplantable mouse hepatomas of different growth rates. Cancer Res 31:743–751

    CAS  PubMed  Google Scholar 

  18. Broët P, Romain S, Daver A et al (2001) Thymidine kinase as a proliferative marker: clinical relevance in 1,692 primary breast cancer patients. J Clin Oncol 19:2778–2787

    PubMed  Google Scholar 

  19. Foekens JA, Romain S, Look M et al (2001) Thymidine kinase and thymidylate synthase in advanced breast cancer: response to tamoxifen and chemotherapy. Cancer Res 61:1421–1425

    CAS  PubMed  Google Scholar 

  20. He Q, Skog S, Fornander T et al (2006) Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following operation of early breast cancer patients. Anticancer Res 26:4753–4760

    CAS  PubMed  Google Scholar 

  21. He Q, Zhang P, Zou L et al (2005) Concentration of thymidine kinase 1 in serum (S-TK1) is a more sensitive proliferation marker in human solid tumors than its activity. Oncol Rep 14:1013–1019

    CAS  PubMed  Google Scholar 

  22. Zhang J, Jia Q, Zou S et al (2006) Thymidine kinase 1: a proliferation marker for determining prognosis and monitoring the surgical outcome of primary bladder carcinoma patients. Oncol Rep 15:455–461

    CAS  PubMed  Google Scholar 

  23. Greene FL, Page DL, Fleming ID et al (2002) AJCC cancer staging manual. Springer, New York

    Book  Google Scholar 

  24. Xu XH, Zhang YM, Shu XH et al (2008) Serological thymidine kinase 1 reflects progression of pre-malignant and malignant tumours during therapy. Mol Med Rep 1:705–711

    CAS  Google Scholar 

  25. Wu CJ, Yang RJ, Zhou J et al (2003) Production and characterisation of a novel chicken IgY antibody raised against C-terminal peptide from human thymidine kinase 1. J Immunol Methods 277:157–169

    Article  CAS  PubMed  Google Scholar 

  26. Topolcan O, Holubeck L (2008) The role of thymidine kinase 1 in cancer diseases. Expert Opin Diagn 2:129–141

    Article  CAS  Google Scholar 

  27. He Q, Zou L, Zhang PA, Lui JX et al (2000) The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TK1 antibody. Int J Biol Markers 15:139–146

    CAS  PubMed  Google Scholar 

  28. Zou L, Zhang PG, Zou S et al (2002) The half-life of cytosolic thymidine kinase in serum by ECL dot bolt: a potential marker for monitoring the response to surgery of patients with gastric cancer. Int J Biol Markers 17:135–140

    CAS  PubMed  Google Scholar 

  29. Li HX, Zhang S, Lei DS et al (2005) Serum thymidine kinase 1 (STK1) is a prognostic and monitoring factor in patients with non-small-cell lung cancer. Oncol Rep 13:145–149

    CAS  PubMed  Google Scholar 

  30. HengZhi C, Zhou H, Tian NB et al (2008) Serological thymidine kinase 1 (STK1) indicates an elevated risk for development of malignant tumors. Anticancer Res 28:3897–3908

    Google Scholar 

  31. Di Raimondo F, Giustolisi R, Lerner S et al (2001) Retrospective study of the prognostic role of serum thymidine kinase level in CLL patients with active disease treated with fludarabine. Ann Oncol 12:621–625

    Article  CAS  PubMed  Google Scholar 

  32. Topolcan O, Holubec L Jr, Finek J et al (2005) Changes of thymidine kinase (TK) during adjuvant and palliative chemotherapy. Anticancer Res 25:1831–1833

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This investigation was supported by Fujian Cancer Hospital of Fujian Medical University Teaching Hospital, Fujian Province, China, and by SSTK Bio-Tech Ltd., Shenzhen, and S.W.S. Medical-Tech. Ltd., Fujian, China.

Conflict of interest statement

None.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yan Chen or Sven Skog.

Appendix

Appendix

See Table 8.

Table 8 Number of patients in the various groups analyzed

About this article

Cite this article

Chen, Y., Ying, M., Chen, Y. et al. Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings. Int J Clin Oncol 15, 359–368 (2010). https://doi.org/10.1007/s10147-010-0067-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-010-0067-4

Keywords

Navigation