Guanylyl Cyclase C as a tumor marker for detection of circulating tumor cells in the peripheral blood of colorectal cancer patients

Meysam Moghbeli, Somaye Chavoshi, Mahmud Tavallaie, Ezzat Dadkhah, Reza Raeissosadati, Moein Farshchian, Mohsen Towliat Kashani, Azita Ganji, Ali Jangjoo, Samaneh Bromand Noughabi, Mohammad Reza Abbaszadegan


Purpose: Guanylyl cyclase C (GCC) is one of the most frequent tumor markers to detect the circulating tumor cells (CTCs) in peripheral blood of colorectal cancer (CRC) patients. It has been proposed as a new marker for the molecular staging of CRC. The level of GCC mRNA expression in peripheral blood of CRC patients was evaluated to explore its probable correlations with the clinicopathological features.

Methods: Relative quantitative expression analysis of GCC mRNA was performed on 80 blood samples (40 patients and 40 normal) using the Real-time RT-PCR.

Results: GCC mRNA expression was detected in 70% of the CRC blood samples. The level of GCC mRNA expression in peripheral blood of patients was significantly higher than that in the normal cases (p = 0.031). Moreover, there was a significant correlation between the GCC copy number and advanced stages of tumor (p = 0.041). Furthermore, we have observed a significant correlation between tumor sizes and GCC copy numbers (p = 0.050).

Conclusion: GCC can be a useful marker not only for detection of CTCs in CRC blood samples, but also for the molecular staging of colorectal cancer. 


Guanylyl cyclase C, Colorectal cancer, Peripheral blood, Tumor marker, Circulating tumor cells

Full Text:



Nugent M, Miller N, Kerin MJ. MicroRNAs in colorectal cancer: function, dysregulation and potential as novel biomarkers. Eur J Surg Oncol. 37(8):649-54.

Soreide K, Nedrebo BS, Knapp JC, et al. Evolving molecular classification by genomic and proteomic biomarkers in colorectal cancer: potential implications for the surgical oncologist. Surg Oncol. 2009;18 (1):31-50.

Boyle P, Langman JS. ABC of colorectal cancer: Epidemiology. Bmj. 2000;321(7264):805-8.

Abdifard E, Ghaderi S, Hosseini S, et al. Incidence trends of colorectal cancer in the West of Iran during 2000-2005. Asian Pac J Cancer Prev. 2000;14(3):1807-11.

Azadeh S, Moghimi-Dehkordi B, Fatem SR, et al. Colorectal cancer in Iran: an epidemiological study. Asian Pac J Cancer Prev. 2008;9(1):123-6.

Mousavi SM, Gouya MM, Ramazani R, et al. Cancer incidence and mortality in Iran. Ann Oncol. 2009;20(3):556-63.

Roya N, Abbas B. Colorectal cancer trends in Kerman province, the largest province in Iran, with forecasting until 2016. Asian Pac J Cancer Prev. 2016;14(2):791-3.

Compton CC, Greene FL. The staging of colorectal cancer: and beyond. CA Cancer J Clin. 2004;54 (6):295-308.

Cunningham D, Atkin W, Lenz HJ, et al. Colorectal cancer. Lancet. 375(9719):1030-47.

Bustin SA, Mueller R. Real-time reverse transcription PCR and the detection of occult disease in colorectal cancer. Mol Aspects Med. 2006;27(2-3):192-223.

Bustin SA, Dorudi S. Molecular assessment of tumour stage and disease recurrence using PCR-based assays. Mol Med Today. 1998;4(9):389-96.

Calaluce R, Miedema BW, Yesus YW. Micrometastasis in colorectal carcinoma: a review. J Surg Oncol. 1998;67 (3):194-202.

Baisse B, Bouzourene H, Saraga EP, et al. Intratumor genetic heterogeneity in advanced human colorectal adenocarcinoma. Int J Cancer. 2001;93(3):346-52.

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

Chevinsky AH. CEA in tumors of other than colorectal origin. Semin Surg Oncol. 1991;7(3):162-6.

Munjal DD, Picken J, Pritchard J. Combined measurement and significance of lipid-bound sialic acid and carcinoembryonic antigen in detection of human cancer. Diagn Immunol. 1984;2(1):36-43.

Okada M, Nishio W, Sakamoto T, et al. Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1,000 consecutive resections for clinical stage I disease. Ann Thorac Surg. 2004;78(1):216-21.

Bustin SA, Gyselman VG, Williams NS, et al. Detection of cytokeratins 19/20 and guanylyl cyclase C in peripheral blood of colorectal cancer patients. Br J Cancer. 1999;79(11-12):1813-20.

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 USA. 1996;93(25):14827-32.

Vlems FA, Diepstra JH, Cornelissen IM, et al. Investigations for a multi-marker RT-PCR to improve sensitivity of disseminated tumor cell detection. Anticancer Res. 2003;23(1A):179-86.

Mejia A, Waldmana SA. Previstage GCC test for staging patients with colorectal cancer. Expert Rev Mol Diagn. 2008;8(5):571-8.

Frick GS, Pitari GM, Weinberg DS, et al. Guanylyl cyclase C: a molecular marker for staging and postoperative surveillance of patients with colorectal cancer. Expert Rev Mol Diagn. 2005;5(5):701-13.

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(3):310-5.

Ohlsson L, Hammarstrom ML, Israelsson A, et al. Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR. Br J Cancer. 2006;95 (2):218-25.

Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17(6):1471-4.

Ardalan Khales S, Abbaszadegan MR, Abdollahi A, et al. SALL4 as a new biomarker for early colorectal cancers. J Cancer Res Clin Oncol. 141(2):229-35.

Raeisossadati R, Farshchian M, Ganji A, et al. Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients. Int J Colorectal Dis. 26(10):1265-70.

Forghanifard MM, Moghbeli M, Raeisossadati R, et al. Role of SALL4 in the progression and metastasis of colorectal cancer. J Biomed Sci. 20:6.

Raeisossadati R, Abbaszadegan MR, Moghbeli M, et al. Aberrant expression of DPPA2 and HIWI genes in colorectal cancer and their impacts on poor prognosis. Tumour Biol. 35(6):5299-305.

Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62(1):10-29.

Newton KF, Newman W, Hill J. Review of biomarkers in colorectal cancer. Colorectal Dis. 14(1):3-17.

Lurje G, Schiesser M, Claudius A, et al. Circulating tumor cells in gastrointestinal malignancies: current techniques and clinical implications. J Oncol. 2010:392652.

Silva JM, Rodriguez R, Garcia JM, et al. Detection of epithelial tumour RNA in the plasma of colon cancer patients is associated with advanced stages and circulating tumour cells. Gut. 2002;50(4):530-4.

Shen C, Hu L, Xia L, et al. Quantitative real-time RT-PCR detection for survivin, CK20 and CEA in peripheral blood of colorectal cancer patients. Jpn J Clin Oncol. 2008;38(11):770-6.

Carrithers SL, Parkinson SJ, Goldstein SD, et al. Escherichia coli heat-stable enterotoxin receptors. A novel marker for colorectal tumors. Dis Colon Rectum. 1996;39(2):171-81.

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(15):4545-52.

Waldman SA, Hyslop T, Schulz S, et al. Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer. Jama. 2009;301(7):745-52.

Camci C, Sahin 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. Tumour Biol. 32(6):1265-70.

Liu Y, Qian J, Feng JG, et al. Detection of circulating tumor cells in peripheral blood of colorectal cancer patients without distant organ metastases. Cell Oncol (Dordr). 36(1):43-53.


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.


International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)

© International Journal of Cancer Therapy and Oncology (IJCTO)

To make sure that you can receive messages from us, please add the '' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.


Number of visits since October, 2013