Skip to main content
SpringerLink
Log in

Evaluation of preoperative serum markers for individual patient prognosis in stage I–III rectal cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

Several independent serum biomarkers have been proposed as prognostic and/or predictive markers for colorectal cancer (CRC). To this date, carcinoembryonic antigen (CEA) remains the only recommended serological CRC biomarker. The present retrospective analysis investigates the prognostic value of several serum markers. A total of 256 patients with rectal cancer underwent surgery for curative intent in a university cancer center between January 1988 and June 2007. Preoperative serum was retrospectively analyzed for albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin, bilirubin, CA 125, cancer antigen 19-9, cancer antigen 72-4 (CA 72-4), CEA, CRP, CYFRA 21-1, ferritin, gamma-glutamyl transpeptidase, glutamate oxaloacetate transanunase, glutamate pyruvate transaminase, hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate-dehydrogenase, serum amyloid A (SAA), and 25-hydroxyvitamin D. Cancer-specific survival (CSS) and disease-free survival (DFS) were estimated. Median follow-up time was 8.4 years. Overall 3- and 5-year CSS was 88.6 and 78.9 %, respectively. DFS rates were 72.8 % (3 years) and 67.5 % (5 years). Univariate analysis of CSS indicated aP, CA 72-4, CEA, and SAA as prognostic factors, while aP, CEA, and SAA were also prognostic with regard to DFS. Multivariate analysis confirmed SAA together with T and N stage as prognostic factors. According to UICC stage, CEA and SAA add prognostic value in stages II and III with regard to DFS and CSS, respectively. The combined use of CEA and SAA is able to identify patients with favorable and poor prognosis. In addition to tumor baseline parameters, routine analysis of SAA together with CEA provided markedly improved prognostic value on CSS and DFS in resected rectal cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay J et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.

    Article  CAS  PubMed  Google Scholar 

  2. Duffy MJ et al. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use. Eur J Cancer. 2007;43(9):1348–60.

    Article  CAS  PubMed  Google Scholar 

  3. Locker GY et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313–27.

    Article  CAS  PubMed  Google Scholar 

  4. Yamashita K, Watanabe M. Clinical significance of tumor markers and an emerging perspective on colorectal cancer. Cancer Sci. 2009;100(2):195–9.

    Article  CAS  PubMed  Google Scholar 

  5. Van Cutsem E et al. Advanced colorectal cancer: ESMO Clinical Practice Guidelines for treatment. Ann Oncol. 2010;21 suppl 5:v93–7.

    Article  PubMed  Google Scholar 

  6. Locker GY et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313–27.

    Article  CAS  PubMed  Google Scholar 

  7. Behbehani AI et al. Prognostic significance of CEA and CA 19-9 in colorectal cancer in Kuwait. Int J Biol Markers. 2000;15(1):51–5.

    CAS  PubMed  Google Scholar 

  8. Reiter W et al. Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer. Anticancer Res. 2000;20(6D):5195–8.

    CAS  PubMed  Google Scholar 

  9. Hofmann, D., et al., Prognosis in non-metastatic colorectal cancer: multivariate evaluation of preoperative levels of six tumor markers in addition to clinical parameters, in LaboratoriumsMedizin2007. p. 76.

  10. Louhimo J et al. Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal cancer. Int J Cancer. 2002;101(6):545–8.

    Article  PubMed  Google Scholar 

  11. Webb A et al. The prognostic value of CEA, beta HCG, AFP, CA125, CA19-9 and C-erb B-2, beta HCG immunohistochemistry in advanced colorectal cancer. Ann Oncol. 1995;6(6):581–7.

    CAS  PubMed  Google Scholar 

  12. Holdenrieder S et al. Cytokeratin serum biomarkers in patients with colorectal cancer. Anticancer Res. 2012;32(5):1971–6.

    CAS  PubMed  Google Scholar 

  13. Biran H et al. Serum amyloid A (SAA) variations in patients with cancer: correlation with disease activity, stage, primary site, and prognosis. J Clin Pathol. 1986;39(7):794–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Bystrom P et al. Evaluation of predictive markers for patients with advanced colorectal cancer. Acta Oncol. 2012;51(7):849–59.

    Article  PubMed  Google Scholar 

  15. Glojnaric I et al. Serum amyloid A protein (SAA) in colorectal carcinoma. Clin Chem Lab Med. 2001;39(2):129–33.

    Article  CAS  PubMed  Google Scholar 

  16. Hansen, M.T., et al., A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4. Oncogene, 2014.

  17. McShane LM et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). Eur J Cancer. 2005;41(12):1690–6.

    Article  PubMed  Google Scholar 

  18. Modest DP et al. Outcome of patients with metastatic colorectal cancer depends on the primary tumor site (midgut vs. hindgut): analysis of the FIRE1-trial (FuFIRI or mIROX as first-line treatment). Anti-Cancer Drugs. 2014;25(2):212–8.

    Article  CAS  PubMed  Google Scholar 

  19. Schmoll HJ et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479–516.

    Article  CAS  PubMed  Google Scholar 

  20. Harrell Jr FE et al. Regression modelling strategies for improved prognostic prediction. Stat Med. 1984;3(2):143–52.

    Article  PubMed  Google Scholar 

  21. Park YJ et al. Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases. World J Surg. 1999;23(7):721–6.

    Article  CAS  PubMed  Google Scholar 

  22. Park YJ et al. Experience of 1446 rectal cancer patients in Korea and analysis of prognostic factors. Int J Color Dis. 1999;14(2):101–6.

    Article  Google Scholar 

  23. Malle E, Sodin-Semrl S, Kovacevic A. Serum amyloid A: an acute-phase protein involved in tumour pathogenesis. Cell Mol Life Sci. 2009;66(1):9–26.

    Article  CAS  PubMed  Google Scholar 

  24. Shiels, M.S., et al., Circulating inflammation markers and prospective risk of lung cancer. J Natl Cancer Inst, 2013;105(24):1871-80.

  25. Toriola AT et al. Biomarkers of inflammation are associated with colorectal cancer risk in women but are not suitable as early detection markers. Int J Cancer. 2013;132(11):2648–58.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Stotz M et al. The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer. Br J Cancer. 2014;110(2):435–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Spencer SK et al. Prognostic/predictive value of 207 serum factors in colorectal cancer treated with cediranib and/or chemotherapy. Br J Cancer. 2013;109(11):2765–73.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Mehrkhani F et al. Prognostic factors in survival of colorectal cancer patients after surgery. Color Dis. 2009;11(2):157–61.

    Article  CAS  Google Scholar 

  29. Stocchi L et al. Impact of surgical and pathologic variables in rectal cancer: a United States community and cooperative group report. J Clin Oncol. 2001;19(18):3895–902.

    CAS  PubMed  Google Scholar 

  30. Ng K et al. Circulating 25-hydroxyvitamin d levels and survival in patients with colorectal cancer. J Clin Oncol. 2008;26(18):2984–91.

    Article  CAS  PubMed  Google Scholar 

  31. Zgaga, L., et al., Plasma vitamin D concentration influences survival outcome after a diagnosis of colorectal cancer. Journal of Clinical Oncology, 2014.Jul 7. pii: JCO.2013.54.5947. [Epub ahead of print]

Download references

Acknowledgments

The authors thank Matthias Wolff for expert secretarial assistance. No direct or indirect funding was received for this study.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany

    Clemens Giessen, Maria Glas, Dominik Paul Modest, Marlies Michl, Volker Heinemann & Christoph Schulz

  2. Institute of Laboratory Medicine, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany

    Dorothea Nagel & Petra Stieber

  3. Department of Surgery, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany

    Fritz Spelsberg & Ulla Lau-Werner

Authors
  1. Clemens Giessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dorothea Nagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Glas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fritz Spelsberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ulla Lau-Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dominik Paul Modest
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marlies Michl
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Volker Heinemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Petra Stieber
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christoph Schulz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clemens Giessen.

Additional information

Clemens Giessen and Dorothea Nagel contributed equally to this work. Petra Stieber and Christoph Schulz contributed equally to this work.

This work was presented in part at the International Society of Oncology and Biomarkers (ISOBM) Annual Meeting 2011 in Florence, Italy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giessen, C., Nagel, D., Glas, M. et al. Evaluation of preoperative serum markers for individual patient prognosis in stage I–III rectal cancer. Tumor Biol. 35, 10237–10248 (2014). https://doi.org/10.1007/s13277-014-2338-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2338-6

Keywords

Search

Navigation