Skip to main content
SpringerLink
Log in

Peripheral blood guanylyl cyclase c (GCC) expressions are associated with prognostic parameters and response to therapy in colorectal cancer patients

  • Research Article
  • Published:
Tumor Biology

Abstract

Guanylyl cyclase C (GCC) is expressed exclusively in normal intestinal mucosal cells, primary and metastatic colorectal cancers (CRC). The aim of this study was to determine the possible association between the GCC expressions in peripheral blood, prognostic parameters and response to chemotherapy in CRC patients. Fourty-nine metastatic CRC patients and 41 healthy controls with similar age and sex were included to this study. Peripheral blood GCC expressions are measured by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Interstingly, no GCC expression was measured in healthy controls but GCC expressions of the patients were detectable. Although there was a significant reduction in GCC expressions in 30 patients with regression (from 5.46 ± 4.12 to 0.06 ± 0.03, p < 0.0001), marked increase in GCC expressions was observed in 19 patients with progression following chemotherapy (from 0.43 ± 0.19 to 1.38 ± 0.52, p = 0.0174). Significant correlation was found between the GCC expressions and carbohydrate antigen 19–9 (CA19-9) levels (p = 0.0041) in 30 patients with regression before chemotherapy. Marked correlation was also detected between the GCC expressions and carcinoembryonic antigen (CEA) levels (p = 0.0072) in 19 patients with progression before chemotherapy. The results of the present study suggest that peripheral blood GCC expressions along with CEA and CA19-9 can be used to determine the early respose to chemotherapy in patients with metastatic CRC. These findings imply that higher expression of GCC in peripheral blood seems to be an indicator of good therapeutic response to chemotherapy and remission. Monitoring the peripheral blood GCC expressions may allow employing different treatment options to metastatic CRC patients.

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

Similar content being viewed by others

References

  1. Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–23.

    Article  PubMed  CAS  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  PubMed  CAS  Google Scholar 

  3. Tatar M, Tatar F. Colorectal cancer in Turkey: current situation and challenges for the future. Eur J Health Econ. 2010;10:99–105.

    Article  Google Scholar 

  4. Wilson PM, Labonte MJ, Lenz HJ. Molecular markers in the treatment of metastatic colorectal cancer. Cancer J. 2010;16:262–72.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Bełtowski J. Guanylin and related peptides. J Physiol Pharmacol. 2001;52:351–75.

    PubMed  Google Scholar 

  7. Forte LR. A novel role for uroguanylin in the regulation of sodium balance. J Clin Invest. 2003;112:1138–41.

    PubMed  CAS  Google Scholar 

  8. Padayatti PS, Pattanaik P, Ma X, van den Akker F. Structural insights into the regulation and the activation mechanism of mammalian guanylyl cyclases. Pharmacol Ther. 2004;104:83–99.

    Article  PubMed  CAS  Google Scholar 

  9. Camici M. Guanylin peptides and colorectal cancer (CRC). Biomed Pharmacother. 2008;62:70–6.

    Article  PubMed  CAS  Google Scholar 

  10. Liu D, Overbey D, Watkinson LD, et al. In vivo imaging of human colorectal cancer using radiolabeled analogs of the uroguanylin peptide hormone. Anticancer Res. 2009;29:3777–83.

    PubMed  CAS  Google Scholar 

  11. Cagir B, Gelmann A, Park J, et al. Guanylyl cyclase C messenger RNA is a biomarker for recurrent stage II colorectal cancer. Ann Intern Med. 1999;131:805–12.

    PubMed  CAS  Google Scholar 

  12. Carrithers SL, Parkinson SJ, Goldstein SD, Park PK, Urbanski RW, Waldman SA. Escherichia coli heat-stable enterotoxin receptors. A novel marker for colorectal tumors. Dis Colon Rectum. 1996;39:171–81.

    Article  PubMed  CAS  Google Scholar 

  13. Waldman SA, Cagir B, Rakinic J, et al. Use of guanylyl cyclase C for detecting micrometastases in lymph nodes of patients with colon cancer. Dis Colon Rectum. 1998;41:310–5.

    Article  PubMed  CAS  Google Scholar 

  14. Schulz S, Hyslop T, Haaf J, et al. A validated quantitative assay to detect occult micrometastases by reverse transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with colorectal cancer. Clin Cancer Res. 2006;12:4545–52.

    Article  PubMed  CAS  Google Scholar 

  15. Saif MW, Chu E. Biology of colorectal cancer. Cancer J. 2010;16:196–201.

    Article  PubMed  CAS  Google Scholar 

  16. Bustin SA, Gyselman VG, Williams NS, Dorudi S. Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of colorectal cancer patients. Br J Cancer. 1999;79:1813–20.

    Article  PubMed  CAS  Google Scholar 

  17. Tien YW, Chang KJ, Jeng YM, et al. Tumor angiogenesis and its possible role in intravasation of colorectal epithelial cells. Clin Cancer Res. 2001;7:1627–32.

    PubMed  CAS  Google Scholar 

  18. Guarino A, Cohen MB, Overmann G, Thompson MR, Giannella RA. Binding of E. coli heat-stable enterotoxin to rat intestinal brush borders and to basolateral membranes. Dig Dis Sci. 1987;32:1017–26.

    Article  PubMed  CAS  Google Scholar 

  19. Drewett JG, Garbers DL. The family of guanylyl cyclase receptors and their ligands. Endocr Rev. 1994;15:135–62.

    PubMed  CAS  Google Scholar 

  20. Carrithers SL, Parkinson SJ, Goldstein S, Park P, Robertson DC, Waldman SA. Escherichia coli heat-stable toxin receptors in human colonic tumors. Gastroenterology. 1994;107:1653–61.

    PubMed  CAS  Google Scholar 

  21. Carrithers SL, Barber MT, Biswas S, et al. Guanylyl cyclase C is a selective marker for metastatic colorectal tumors in human extraintestinal tissues. Proc Natl Acad Sci U S A. 1996;93:14827–32.

    Article  PubMed  CAS  Google Scholar 

  22. Chang C, Marszlowicz G, Waldman Z, et al. Guanylyl cyclase C as a biomarker for targeted imaging and therapy of metastatic colorectal cancer. Biomark Med. 2009;3:33–45.

    Article  PubMed  CAS  Google Scholar 

  23. Liefers GJ, Cleton-Jansen AM, van de Velde CJ, et al. Micrometastases and survival in stage II colorectal cancer. N Engl J Med. 1998;339:223–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by a project (BAP TF.09.11) from the University of Gaziantep.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Faculty of Medicine, University of Gaziantep, Gaziantep Oncology Hospital, 27310, Gaziantep, Turkey

    Celalettin Camci, Akif Şahin, Alper Sevinc, Mehmet E. Kalender & Özlem N. Sever

  2. Department of Medical Biology and Genetics, Faculty of Medicine, University of Gaziantep, Gaziantep, 27310, Turkey

    Serdar Öztuzcu & Esma Özkara

  3. Department of Medical Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep, 27310, Turkey

    Abdullah T. Demiryürek

Authors
  1. Celalettin Camci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akif Şahin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alper Sevinc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehmet E. Kalender
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Serdar Öztuzcu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Özlem N. Sever
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Esma Özkara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Abdullah T. Demiryürek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Celalettin Camci.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Camci, C., Şahin, A., Sevinc, A. et al. Peripheral blood guanylyl cyclase c (GCC) expressions are associated with prognostic parameters and response to therapy in colorectal cancer patients. Tumor Biol. 32, 1265–1270 (2011). https://doi.org/10.1007/s13277-011-0231-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-011-0231-0

Keywords

Search

Navigation