Tumor Biology

, Volume 36, Issue 10, pp 7897–7906 | Cite as

Preoperative serum markers for individual patient prognosis in stage I–III colon cancer

  • Clemens Giessen-JungEmail author
  • Dorothea Nagel
  • Maria Glas
  • Fritz Spelsberg
  • Ulla Lau-Werner
  • Dominik Paul Modest
  • Christoph Schulz
  • Volker Heinemann
  • Dorit Di Gioia
  • Petra Stieber
Research Article


Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (βhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve risk-adapted post-op surveillance.


Colorectal cancer Tumor marker CEA CA 19-9 Gamma-glutamyltransferase Prognostic factors 



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

Conflicts of interest



  1. 1.
    Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403.CrossRefPubMedGoogle Scholar
  2. 2.
    Duffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, 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.CrossRefPubMedGoogle Scholar
  3. 3.
    Yamashita K, Watanabe M. Clinical significance of tumor markers and an emerging perspective on colorectal cancer. Cancer Sci. 2009;100(2):195–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Van Cutsem E, Nordlinger B, Cervantes A, Group ObotEGW. Advanced colorectal cancer: ESMO Clinical Practice Guidelines for treatment. Annals of Oncology. 2010;21 suppl 5:v93–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Spencer SK, Pommier AJ, Morgan SR, Barry ST, Robertson JD, Hoff PM, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313–27.CrossRefPubMedGoogle Scholar
  7. 7.
    Behbehani AI, Al-Sayer H, Farghaly M, Kanawati N, Mathew A, al-Bader A, et al. Prognostic significance of CEA and CA 19-9 in colorectal cancer in Kuwait. Int J Biol Markers. 2000;15(1):51–5.PubMedGoogle Scholar
  8. 8.
    Reiter W, Stieber P, Reuter C, Nagel D, Lau-Werner U, Lamerz R. Multivariate analysis of the prognostic value of CEA and CA 19-9 serum levels in colorectal cancer. Anticancer Res. 2000;20(6D):5195–8.PubMedGoogle Scholar
  9. 9.
    Hofmann D, Nagel D, Lau-Werner U, Wichmann Matthias W, Hornung H-M, Stenman Ulf H, et al. Prognosis in non-metastatic colorectal cancer: multivariate evaluation of preoperative levels of six tumor markers in addition to clinical parameters. Lab Med. 2007. p. 76.Google Scholar
  10. 10.
    Louhimo J, Carpelan-Holmstrom M, Alfthan H, Stenman UH, Jarvinen HJ, Haglund C. Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal cancer. Int J Cancer. 2002;101(6):545–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Yang XQ, Chen C, Hou JX, Peng CW, Huang CQ, Li Y. Preoperative serum carbohydrate antigen 242 is a useful predictive and prognostic marker in colorectal cancer. Hepatogastroenterology. 2011;58(106):377–82.PubMedGoogle Scholar
  12. 12.
    Webb A, Scott-Mackie P, Cunningham D, Norman A, Andreyev J, O'Brien M, 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.CrossRefPubMedGoogle Scholar
  13. 13.
    Holdenrieder S, Stieber P, Liska V, Treska V, Topolcan O, Dreslerova J, et al. Cytokeratin serum biomarkers in patients with colorectal cancer. Anticancer Res. 2012;32(5):1971–6.PubMedGoogle Scholar
  14. 14.
    Proctor MJ, Talwar D, Balmar SM, O'Reilly DS, Foulis AK, Horgan PG, et al. The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow Inflammation Outcome Study. Br J Cancer. 2010;103(6):870–6.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Tsuboya T, Kuriyama S, Nagai M, Hozawa A, Sugawara Y, Tomata Y, et al. Gamma-glutamyltransferase and cancer incidence: the Ohsaki cohort study. J Epidemiol. 2012;22(2):144–50.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM. REporting recommendations for tumour MARKer prognostic studies (REMARK). Eur J Cancer. 2005;41(12):1690–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Giessen C, Nagel D, Glas M, Spelsberg F, Lau-Werner U, Modest DP, et al. Evaluation of preoperative serum markers for individual patient prognosis in stage I–III rectal cancer. Tumour Biol. 2014;35(10):10237–48.CrossRefPubMedGoogle Scholar
  18. 18.
    Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, 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.CrossRefPubMedGoogle Scholar
  19. 19.
    Park YJ, Park KJ, Park JG, Lee KU, Choe KJ, Kim JP. Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases. World J Surg. 1999;23(7):721–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Park YJ, Youk EG, Choi HS, Han SU, Park KJ, Lee KU, et al. Experience of 1446 rectal cancer patients in Korea and analysis of prognostic factors. Int J Color Dis. 1999;14(2):101–6.CrossRefGoogle Scholar
  21. 21.
    Mehrkhani F, Nasiri S, Donboli K, Meysamie A, Hedayat A. Prognostic factors in survival of colorectal cancer patients after surgery. Color Dis. 2009;11(2):157–61.CrossRefGoogle Scholar
  22. 22.
    Chau I, Allen MJ, Cunningham D, Norman AR, Brown G, Ford HE, et al. The value of routine serum carcino-embryonic antigen measurement and computed tomography in the surveillance of patients after adjuvant chemotherapy for colorectal cancer. J Clin Oncol. 2004;22(8):1420–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A. Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum. 1998;41(9):1127–33.CrossRefPubMedGoogle Scholar
  24. 24.
    Stocchi L, Nelson H, Sargent DJ, O'Connell MJ, Tepper JE, Krook JE, et al. Impact of surgical and pathologic variables in rectal cancer: a United States community and cooperative group report. J Clin Oncol Off J Am Soc Clin Oncol. 2001;19(18):3895–902.CrossRefGoogle Scholar
  25. 25.
    Hochwald SN, Harrison LE, Rose DM, Anderson M, Burt ME. gamma-Glutamyl transpeptidase mediation of tumor glutathione utilization in vivo. J Natl Cancer Inst. 1996;88(3-4):193–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhu Y, Yang SR, Wang PP, Savas S, Wish T, Zhao J, et al. Influence of pre-diagnostic cigarette smoking on colorectal cancer survival: overall and by tumour molecular phenotype. Br J Cancer. 2014;110(5):1359–66.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Steele SR, Park GE, Johnson EK, Martin MJ, Stojadinovic A, Maykel JA, et al. The impact of age on colorectal cancer incidence, treatment, and outcomes in an equal-access health care system. Dis Colon Rectum. 2014;57(3):303–10.CrossRefPubMedGoogle Scholar
  28. 28.
    Jafri SH, Mills G. Lifestyle modification in colorectal cancer patients: an integrative oncology approach. Future Oncol. 2013;9(2):207–18.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Clemens Giessen-Jung
    • 1
    Email author
  • Dorothea Nagel
    • 2
  • Maria Glas
    • 1
  • Fritz Spelsberg
    • 3
  • Ulla Lau-Werner
    • 3
  • Dominik Paul Modest
    • 1
  • Christoph Schulz
    • 1
  • Volker Heinemann
    • 1
  • Dorit Di Gioia
    • 1
  • Petra Stieber
    • 2
  1. 1.Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer CenterUniversity of MunichMunichGermany
  2. 2.Institute of Laboratory Medicine, Klinikum GrosshadernUniversity of MunichMunichGermany
  3. 3.Department of Surgery, Klinikum GrosshadernUniversity of MunichMunichGermany

Personalised recommendations