Abstract
Aim
Combination of biomarkers may improve diagnosis and have better prognostic value than single markers. The purpose of this study was to investigate whether combined CEA and CD44v6 improves prognostic value in stage I and stage II (stage I/II) colorectal cancer (CRC).
Methods
Preoperative serum CEA level and the expression of CD44v6 in CRC tissues were examined by electrochemiluminescence immunoassay and immunohistochemistry, respectively. The association of CEA and CD44v6 with clinicopathological features and their possible prognostic values was analyzed.
Results
The preoperative elevated serum CEA level and positive CD44v6 expression were detected in 30.1 % (52/173) serum samples and 60.5 % (101/167) CRC tissues, respectively. Patients with an elevated-CEA level or a CD44v6-negative tumor had a worse disease-specific survival (DSS) than those with a normal-CEA level or CD44v6-positive tumor (P = 0.024, P = 0.012, respectively). Moreover, CD44v6 expression could be used in discriminating patients from good to poor prognosis in normal-CEA subgroup (P = 0.043), but not in elevated-CEA subgroup (P = 0.563). Multivariate analysis revealed that combined CEA and CD44v6 was an independent prognostic factor for patients with stage I/II CRC (P = 0.023). However, serum CEA level only retained a borderline significance for correlation with a worse DSS (P = 0.059), and CD44v6 expression alone was not an independent prognostic factor for DSS in multivariate analysis (P = 0.123).
Conclusion
These results suggested that combined CEA/CD44v6 had better prognostic value than CEA or CD44v6 alone for patients with stage I/II CRC.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Zhao P, Dai M, Chen W, Li N. Cancer trends in China. Jpn J Clin Oncol. 2010;40:281–5.
Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61:212–36.
Carlson MR, Previstage GCC. Colorectal cancer staging test: a new molecular test to identify lymph node metastases and provide more accurate information about the stage of patients with colorectal cancer. Mol Diagn Ther. 2009;13:11–4.
Tsikitis VL, Malireddy K, Green EA, Christensen B, Whelan R, Hyder J, et al. Postoperative surveillance recommendations for early stage colon cancer based on results from the clinical outcomes of surgical therapy trial. J Clin Oncol. 2009;27:3671–6.
Shibayama M, Maak M, Nitsche U, Gotoh K, Rosenberg R, Janssen KP. Prediction of metastasis and recurrence in colorectal cancer based on gene expression analysis: ready for the clinic? Cancers. 2011;3:2858–69.
Yu X, McBean AM. Screening mammography use and chemotherapy among female stage II colon cancer patients: a retrospective cohort study. BMC Health Serv Res. 2010;10:98.
Bacolod MD, Barany F. Molecular profiling of colon tumors: the search for clinically relevant biomarkers of progression, prognosis, therapeutics, and predisposition. Ann Surg Oncol. 2011;18:3694–700.
Newton KF, Newman W, Hill J. Review of biomarkers in colorectal cancer. Colorectal Dis. 2012;14:3–17.
Bohanes P, LaBonte MJ, Winder T, Lenz HJ. Predictive molecular classifiers in colorectal cancer. Semin Oncol. 2011;38:576–87.
López-Gómez M, Casado E, Cejas P, Feliu J. Prognostic and predictive factors in colorectal cancer: The importance of reliable markers for effective selection of therapy. In: Esther Uña Cidón editor. The challenge of colorectal cancer: a review book. India: Research Signpost Press; 2011. p. 285–308.
Zlobec I, Baker K, Terracciano L, Peter S, Degen L, Beglinger C, et al. Two-marker protein profile predicts poor prognosis in patients with early rectal cancer. Br J Cancer. 2008;99:1712–7.
Liu C, Qu L, Dong B, Xing X, Ren T, Zeng Y, et al. Combined phenotype of 4 markers improves prognostic value of patients with colon cancer. Am J Med Sci. 2012;343:295–302.
Peng Y, Wang L, Gu J. Elevated preoperative carcinoembryonic antigen (CEA) and Ki67 is predictor of decreased survival in IIA stage colon cancer. World J Surg. 2013;37:208–13.
Li M, Li JY, Zhao AL, He JS, Zhou LX, Li YA, et al. Comparison of carcinoembryonic antigen prognostic value in serum and tumour tissue of patients with colorectal cancer. Colorectal Dis. 2009;11:276–81.
Chen L, Jiang B, Wang Z, Liu M, Ma Y, Yang H, et al. Expression and prognostic significance of GATA-binding protein 2 in colorectal cancer. Med Oncol. 2013;. doi:10.1007/s12032-013-0498-7.
Peng J, Lu JJ, Zhu J, Xu Y, Lu H, Lian P, et al. Prediction of treatment outcome by CD44v6 after total mesorectal excision in locally advanced rectal cancer. Cancer J. 2008;14:54–61.
Gold P, Freedman SO. Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med. 1965;121:439–62.
Sun LC, Chu KS, Cheng SC, Lu CY, Kuo CH, Hsieh JS, et al. Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment. BMC Cancer. 2009;9:288.
Huh JW, Oh BR, Kim HR, Kim YJ. Preoperative carcinoembryonic antigen level as an independent prognostic factor in potentially curative colon cancer. J Surg Oncol. 2010;101:396–400.
Tarantino I, Warschkow R, Worni M, Merati-Kashani K, Köberle D, Schmied BM, et al. Elevated preoperative CEA is associated with worse survival in stage I-III rectal cancer patients. Br J Cancer. 2012;107:266–74.
Fakih MG, Padmanabhan A. CEA monitoring in colorectal cancer. What you should know. Oncology (Williston Park). 2006;20:579–87.
Wanebo HJ, Rao B, Pinsky CM, Hoffman RG, Stearns M, Schwartz MK, et al. Preoperative carcinoembryonic antigen level as a prognostic indicator in colorectal cancer. N Engl J Med. 1978;299:448–51.
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;20:5195–8.
Kirat HT, Ozturk E, Lavery IC, Kiran RP. The predictive value of preoperative carcinoembryonic antigen level in the prognosis of colon cancer. Am J Surg. 2012;204:447–52.
Su BB, Shi H, Wan J. Role of serum carcinoembryonic antigen in the detection of colorectal cancer before and after surgical resection. World J Gastroenterol. 2012;18:2121–6.
Jung T, Gross W, Zöller M. CD44v6 coordinates tumor matrix-triggered motility and apoptosis resistance. J Biol Chem. 2011;286:15862–74.
Wielenga VJ, Heider KH, Offerhaus GJ, Adolf GR, van den Berg FM, Ponta H, et al. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993;53:4754–6.
Saito S, Okabe H, Watanabe M, Ishimoto T, Iwatsuki M, Baba Y, et al. CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer. Oncol Rep. 2013;. doi:10.3892/or.2013.2273.
Zlobec I, Günthert U, Tornillo L, Iezzi G, Baumhoer D, Terracciano L, et al. Systematic assessment of the prognostic impact of membranous CD44v6 protein expression in colorectal cancer. Histopathology. 2009;55:564–75.
Acknowledgments
We thank Dr. Li Sun and Yiqiang Liu for histopathological diagnosis. We thank Dr. Jiabo Di for critical reading of the manuscript. This study was supported by the grants from the National Natural Science Foundation of China (No. 81272766 and No. 81071658), Capital Medical Development and Research Foundation (No. 2009-2093), Clinical Characteristics and Application Research of Capital (Beijing Municipal Science & Technology Commission No. Z121107001012130), Beijing Natural Science Foundation (No. 7132054), New Star of Science and Technology Program of Beijing (Beijing Municipal Science & Technology Commission No. 2011060).
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
L. Chen and B. Jiang contributed equally to this work.
Rights and permissions
About this article
Cite this article
Chen, L., Jiang, B., Wang, Z. et al. Combined preoperative CEA and CD44v6 improves prognostic value in patients with stage I and stage II colorectal cancer. Clin Transl Oncol 16, 285–292 (2014). https://doi.org/10.1007/s12094-013-1069-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-013-1069-2