Role of CDX2 Marker in Patients with Colorectal Cancer

Authors

DOI:

https://doi.org/10.48112/bcs.v2i1.321

Abstract

Abstract Views: 174

CDX2 has been proposed as a tumor suppressor in colon cancer, CDX2 gene is often amplified in colon cancer, there is a lineage survival oncogene function in some tumors, the role of CDX2 protein during CRC development remains debatable. The aim of this study investigate the effect of low CDX2 expression on overall survival (OS) for prognosis of CRC patients and estimate of therapeutic activity of CDX2 expression in predictive of chemotherapy respond. This study done in the Middle Euphrates Unit for Cancer Research, Faculty of Medicine, University of Kufa in Al-Najaf province. This study was carried out on sixty-three cases of CRC in the form of available paraffin blocks who underwent surgical resection between 2015 and 2020. Thirty_ seven blocks of normal non tumoral colorectal tissue collected randomly from archives of two private laboratories during collection of malignant tissue blocks. Nuclear low expression of CDX2 in control and patient groups were 0(0.00%) and 30 (47.6%), while high expression of this protein was 37 (100%) and 33(52.4%) in control and patient groups respectively. OS was longer in patients with low CDX2 protein expression who intake adjuvant chemotherapy (71.33%) with mean survival (24.75±2.81 month) than patients were not intake adjuvant chemotherapy (53.71%) with mean survival (15.227±1.66 month). CDX2 expression regarded as diagnostic marker for non-mucinous CRC. High of CDX2 expression can be used as an independent good prognostic biomarker to predict longer survival of patients with CRC.

Keywords:

CDX2 Marker, Colorectal cancer , Overall survival

Metrics

Metrics Loading ...

References

Asgari-Karchekani, S., Karimian, M., Mazoochi, T., Taheri, M. A., & Khamehchian, T. (2020). CDX2 protein expression in colorectal cancer and itscorrelation with clinical and pathological characteristics, prognosis, and survival rate of patients. Journal of Gastrointestinal Cancer, 51(3), 844-849. https://doi.org/10.1007/s12029-019-00314-w

Bae, J. M., Lee, T. H., Cho, N. Y., Kim, T. Y., & Kang, G. H. (2015). Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients. World journal of gastroenterology: WJG, 21(5), 1457. https://doi.org/10.3748/wjg.v21.i5.1457

Barbareschi, M., Murer, B., Colby, T. V., Chilosi, M., Macri, E., Loda, M., & Doglioni, C. (2003). CDX-2 homeobox gene expression is a reliable marker of colorectal adenocarcinoma metastases to the lungs. The American journal of surgical pathology, 27(2), 141-149.

Bayrak, R., Haltas, H., & Yenidunya, S. (2012). The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody. Diagnostic pathology, 7(1), 1-11. https://doi.org/10.1186/1746-1596-7-9

Beck, F. (2002). Homeobox genes in gut development. Gut, 51(3), 450-454. http://dx.doi.org/10.1136/gut.51.3.450

Böckelman, C., Engelmann, B. E., Kaprio, T., Hansen, T. F., & Glimelius, B. (2015). Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature. Acta oncologica, 54(1), 5-16. https://doi.org/10.3109/0284186X.2014.975839

Bonhomme, C., Duluc, I., Martin, E., Chawengsaksophak, K., Chenard, M. P., Kedinger, M., ... & Domon-Dell, C. (2003). The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development. Gut, 52(10), 1465-1471. http://dx.doi.org/10.1136/gut.52.10.1465

Coskun, M., Troelsen, J. T., & Nielsen, O. H. (2011). The role of CDX2 in intestinal homeostasis and inflammation. Biochimica et biophysica acta (BBA)-Molecular basis of disease, 1812(3), 283-289. https://doi.org/10.1016/j.bbadis.2010.11.008

Dae Hong, K., Lee, D., Lee, Y., Lee, S. I., & Moon, H. Y. (2013). Reduced CDX2 expression predicts poor overall survival in patients with colorectal cancer. The American Surgeon, 79(4), 353-360. https://doi.org/10.1177/000313481307900422

Douglas, E. J., Fiegler, H., Rowan, A., Halford, S., Bicknell, D. C., Bodmer, W., ... & Carter, N. P. (2004). Array comparative genomic hybridization analysis of colorectal cancer cell lines and primary carcinomas. Cancer research, 64(14), 4817-4825. https://doi.org/10.1158/0008-5472.CAN-04-0328

Gao, N., White, P., & Kaestner, K. H. (2009). Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2. Developmental cell, 16(4), 588-599. https://doi.org/10.1016/j.devcel.2009.02.010

Guo, R. J., Suh, E. R., & Lynch, J. P. (2004). The role of Cdx proteins in intestinal development and cancer. Cancer biology & therapy, 3(7), 593-601. https://doi.org/10.4161/cbt.3.7.913

Hinoi, T., Loda, M., & Fearon, E. R. (2003). Silencing of CDX2 expression in colon cancer via a dominant repression pathway. Journal of Biological Chemistry, 278(45), 44608-44616. https://doi.org/10.1074/jbc.M307435200

Hinoi, T., Tani, M., Lucas, P. C., Caca, K., Dunn, R. L., Macri, E., ... & Fearon, E. R. (2001). Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. The American journal of pathology, 159(6), 2239-2248. https://doi.org/10.1016/S0002-9440(10)63074-X

Kojima, M., Morisaki, T., Sasaki, N., Nakano, K., Mibu, R., Tanaka, M., & Katano, M. (2004). Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression. Anticancer research, 24(2B), 675-682. http://www.ncbi.nlm.nih.gov/pubmed/15161011

Mallo, G. V., Soubeyran, P., Lissitzky, J. C., André, F., Farnarier, C., Marvaldi, J., ... & Iovanna, J. L. (1998). Expression of the Cdx1and Cdx2Homeotic Genes Leads to Reduced Malignancy in Colon Cancer-derived Cells. Journal of Biological Chemistry, 273(22), 14030-14036. https://doi.org/10.1074/jbc.273.22.14030

Matsuda, M., Sentani, K., Noguchi, T., Hinoi, T., Okajima, M., Matsusaki, K., ... & Yasui, W. (2010). Immunohistochemical analysis of colorectal cancer with gastric phenotype: Claudin‐18 is associated with poor prognosis. Pathology international, 60(10), 673-680. https://doi.org/10.1111/j.1440-1827.2010.02587.x

Olsen, J., Espersen, M. L. M., Jess, P., Kirkeby, L. T., & Troelsen, J. T. (2014). The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review. Surgical oncology, 23(3), 167-176. https://doi.org/10.1016/j.suronc.2014.07.003

Ryan, É. J., Creavin, B., Khaw, Y. L., Kelly, M. E., Mohan, H. M., Geraghty, R., ... & Winter, D. C. (2018). Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair-deficient colorectal cancer. BJS open, 2(6), 456-463. https://doi.org/10.1002/bjs5.91

Salari, K., Spulak, M. E., Cuff, J., Forster, A. D., Giacomini, C. P., Huang, S., ... & Pollack, J. R. (2012). CDX2 is an amplified lineage-survival oncogene in colorectal cancer. Proceedings of the National Academy of Sciences, 109(46), E3196-E3205. https://doi.org/10.1073/pnas.1206004109

Sivagnanasundaram, S., Islam, I., Talbot, I., Drummond, F., Walters, J. R. F., & Edwards, Y. H. (2001). The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis. British journal of cancer, 84(2), 218-225. https://doi.org/10.1054/bjoc.2000.1544

Sjoerd, H., de Wit, M., Slebos, R. J., Delis-van Diemen, P. M., Sanders, J., Piersma, S. R., ... & Fijneman, R. J. (2021). Quantitative analysis of CDX2 protein expression improves its clinical utility as a prognostic biomarker in stage II and III colon cancer. European Journal of Cancer, 144, 91-100. https://doi.org/10.1016/j.ejca.2020.10.029

Slattery, M. L., Herrick, J., Wolff, R. K., Caan, B. J., Potter, J. D., & Sweeney, C. (2007). CDX2 VDR polymorphism and colorectal cancer. Cancer Epidemiology Biomarkers & Prevention, 16(12), 2752-2755. https://doi.org/10.1158/1055-9965.EPI-07-2611

Slik, K., Turkki, R., Carpén, O., Kurki, S., Korkeila, E., Sundström, J., & Pellinen, T. (2019). CDX2 loss with microsatellite stable phenotype predicts poor clinical outcome in stage II colorectal carcinoma. The American journal of surgical pathology, 43(11), 1473-1482. https://doi.org/10.1097/PAS.0000000000001356

Su, M. C., Yuan, R. H., Lin, C. Y., & Jeng, Y. M. (2008). Cadherin-17 is a useful diagnostic marker for adenocarcinomas of the digestive system. Modern Pathology, 21(11), 1379-1386. https://doi.org/10.1038/modpathol.2008.107

Sullivan, L. M., Smolkin, M. E., Frierson Jr, H. F., & Galgano, M. T. (2008). Comprehensive evaluation of CDX2 in invasive cervical adenocarcinomas: immunopositivity in the absence of overt colorectal morphology. The American journal of surgical pathology, 32(11), 1608-1612. https://doi.org/10.1097/PAS.0b013e31816d71c4

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209-249. https://doi.org/10.3322/caac.21660

Verzi, M. P., Shin, H., He, H. H., Sulahian, R., Meyer, C. A., Montgomery, R. K., ... & Shivdasani, R. A. (2010). Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2. Developmental cell, 19(5), 713-726. https://doi.org/10.1016/j.devcel.2010.10.006

Xiong, Y., You, W., Hou, M., Peng, L., Zhou, H., & Fu, Z. (2018). Nomogram integrating genomics with clinicopathologic features improves prognosis prediction for colorectal cancer. Molecular Cancer Research, 16(9), 1373-1384. https://doi.org/10.1158/1541-7786.MCR-18-0063

Role of CDX2 Marker in Patients with Colorectal Cancer

Published

2023-01-01

How to Cite

Al-Duhaidahawi, M. (2023). Role of CDX2 Marker in Patients with Colorectal Cancer. Biomedicine and Chemical Sciences, 2(1), 11–15. https://doi.org/10.48112/bcs.v2i1.321

Issue

Section

Articles