Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer

İlknur Çalık; Muhammet Çalık; İbrahim Hanifi Özercan; Adile Ferda Dağlı; Gökhan Artaş; Gülistan Türken; Burcu Sarıkaya

doi:10.5798/dicletip.706005

Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer

Abstract

Objective: Since colorectal cancers (CRC) are tumors with heterogeneous biological behavior, prediction of their prognosis remains challenging. Caudal-related homeobox gene 2 (CDX2), which has important roles in the development and maintenance of intestines, is thought to have tumor suppressing effect on CRCs. The aim of this study was to investigate the prognostic significance of decreased-CDX2 expression. Method: This retrospective study included 224 patients diagnosed with CRC between 2009 and 2014. Paraffinized blocks of these patients were stained with CDX2 immunohistochemically and evaluated semiquantitatively. Results: Only 35 (15.6%) of 224 patients had low-CDX2 expression. Decrease in CDX2 expression was closely associated with classical prognostic parameters such as histopathologic type, histologic grade, lymph node metastasis, distant metastasis, and TNM stage. Patients with decreased-CDX2 expression had more lymph node metastasis (p=0.013) and advanced TNM stage (p=0.004) than those without decreased-expression. The mean survival was 53.0±0.89 months. Cox regression analysis showed that decreased-CDX2 expression was significantly related with overall survival (Univariate analysis; hazard ratio: 0.09, 95% confidence interval: 0.05-0.16; p<0.001; Multivariate analysis; hazard ratio: 0.24, 95% confidence interval: 0.13-0.48; p<0.001) and disease-free survival (Univariate analysis; hazard ratio: 0.80, 95% confidence interval: 0.05-0.13; p<0.001; Multivariate analysis; hazard ratio: 0.15, 95% confidence interval: 0.08-0.25; p<0.001). Conclusion: Decreased CDX2 expression is significantly related with worse biological features and can be used as an independent prognostic biomarker in patients with CRCs.

Keywords

Colorectal cancer,CDX2,prognosis,overall survival

References

1. Haddad FG, Eid R, Kourie HR, Barouky E, Ghosn M. Prognostic and predictive biomarkers in nonmetastatic colorectal cancers. Future Oncol 2018; 14: 2097-102.
2. Akdeniz N, Kaplan MA, Küçüköner M, et al. Prognostic importance of primary tumor location in RAS mutant metastatic colorectal cancer. Dicle Med J 2019; 46: 247-53.
3. Slik K, Turkki R, Carpén O, et al. CDX2 Loss With Microsatellite Stable Phenotype Predicts Poor Clinical Outcome in Stage II Colorectal Carcinoma. Am J SurgPathol 2019; 43: 1473-82.
4. Xiong Y, You W, Hou M, et al. Nomogram Integrating Genomics with Clinicopathologic Features Improves Prognosis Prediction for Colorectal Cancer. Mol Cancer Res 2018; 16: 1373-84.
5. Shigematsu Y, Inamura K, Yamamoto N, et al. Impact of CDX2 expression status on the survival of patients after curative resection for colorectal cancer liver metastasis. BMC Cancer 2018; 18: 980.
6. Shigematsu Y, Inamura K, Mise Y, et al. CDX2 expression is concordant between primary colorectal cancer lesions and corresponding liver metastases independent of chemotherapy: a single-center retrospective study in Japan. Oncotarget 2018; 9: 17056-65.
7. Bae JM, Lee TH, Cho NY, Kim TY, Kang GH. Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients. World J Gastroenterol 2015; 21: 1457-67.
8. Kaimaktchiev V, Terracciano L, Tornillo L, et al. The homeobox intestinal differentiation factor CDX2 is selectively expressed in gastrointestinal adenocarcinomas. Mod Pathol 2004; 17: 1392-99.

9. Hryniuk A, Grainger S, Savory JG, Lohnes D. Cdx1 and Cdx2 function as tumor suppressors. J BiolChem 2014; 289: 33343-54.
10. Matsuda M, Sentani K, Noguchi T, et al. Immunohistochemical analysis of colorectal cancer with gastric phenotype: claudin-18 is associated with poor prognosis. PatholInt 2010; 60: 673-80. 11. Xu W, Zhu Y, Shen W, et al. Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer. J Int Med Res 2019; 47: 1829-42.
12. Hong KD, Lee D, Lee Y, Lee SI, Moon HY. Reduced CDX2 expression predicts poor overall survival in patients with colorectal cancer. Am Surg 2013; 79: 353-60.
13. Hari DM, Leung AM, Lee JH, et al. AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am CollSurg 2013; 217: 181-90.
14. Dalerba P, Sahoo D, Paik S, et al. CDX2 as a prognostic biomarker in stage II and stage III colon cancer. N Engl J Med 2016; 374: 211–22.
15. Olsen J, Espersen ML, Jess P, Kirkeby LT, Troelsen JT. The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review. SurgOncol 2014; 23: 167-76.
16. Hansen TF, Kjaer-Frifeldt S, Eriksen AC, et al. Prognostic impact of CDX2 in stage II colon cancer: results from two nationwide cohorts. Br J Cancer 2018; 119: 1367-73.
17. Lugli A, Tzankov A, Zlobec I, Terracciano LM. Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status. Mod Pathol 2008; 21: 1403-12.
18. Tóth C, Sükösd F, Valicsek E, et al. Loss of CDX2 gene expression is associated with DNA repair proteins and is a crucial member of the Wnt signaling pathway in liver metastasis of colorectal cancer. Oncol Lett 2018; 15: 3586-93.
19. Misiakos EP, Karidis NP and Kouraklis G: Current treatment for colorectal liver metastases. World J Gastroenterol 2011; 17: 4067-75.
20. Baba Y, Nosho K, Shima K, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res 2009; 15: 4665-73.
21. Dawson H, Galván JA, Helbling M, et al. Possible role of Cdx2 in the serrated pathway of colorectal cancer characterized by BRAF mutation, high-level CpG Island methylator phenotype and mismatch repair-deficiency. Int J Cancer 2014; 134: 2342-51.
22. Dawson H, Koelzer VH, Lukesch AC, et al. Loss of Cdx2 Expression in Primary Tumors and Lymph Node Metastases is Specific for Mismatch RepairDeficiency in Colorectal Cancer. Front Oncol 2013; 3: 265.

Details

Primary Language

English

Subjects

Health Care Administration

Journal Section

Research Article

Authors

İlknur Çalık ^* This is me
Türkiye

Muhammet Çalık This is me
Türkiye

İbrahim Hanifi Özercan This is me
Türkiye

Adile Ferda Dağlı This is me
Türkiye

Gökhan Artaş This is me
Türkiye

Gülistan Türken This is me
Türkiye

Burcu Sarıkaya This is me
Türkiye

Publication Date

March 17, 2020

Submission Date

October 19, 2019

Acceptance Date

January 7, 2020

Published in Issue

Year 2020 Volume: 47 Number: 1

DOI

https://doi.org/10.5798/dicletip.706005

IZ

https://izlik.org/JA32UG29CY

Cite

RIS / Bibtex

APA

Çalık, İ., Çalık, M., Özercan, İ. H., Dağlı, A. F., Artaş, G., Türken, G., & Sarıkaya, B. (2020). Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer. Dicle Medical Journal, 47(1), 57-65. https://doi.org/10.5798/dicletip.706005

AMA

1.Çalık İ, Çalık M, Özercan İH, et al. Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer. Dicle Medical Journal. 2020;47(1):57-65. doi:10.5798/dicletip.706005

Chicago

Çalık, İlknur, Muhammet Çalık, İbrahim Hanifi Özercan, et al. 2020. “Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer”. Dicle Medical Journal 47 (1): 57-65. https://doi.org/10.5798/dicletip.706005.

EndNote

Çalık İ, Çalık M, Özercan İH, Dağlı AF, Artaş G, Türken G, Sarıkaya B (March 1, 2020) Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer. Dicle Medical Journal 47 1 57–65.

IEEE

[1]İ. Çalık et al., “Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer”, Dicle Medical Journal, vol. 47, no. 1, pp. 57–65, Mar. 2020, doi: 10.5798/dicletip.706005.

ISNAD

Çalık, İlknur - Çalık, Muhammet - Özercan, İbrahim Hanifi - Dağlı, Adile Ferda - Artaş, Gökhan - Türken, Gülistan - Sarıkaya, Burcu. “Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer”. Dicle Medical Journal 47/1 (March 1, 2020): 57-65. https://doi.org/10.5798/dicletip.706005.

JAMA

1.Çalık İ, Çalık M, Özercan İH, Dağlı AF, Artaş G, Türken G, Sarıkaya B. Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer. Dicle Medical Journal. 2020;47:57–65.

MLA

Çalık, İlknur, et al. “Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer”. Dicle Medical Journal, vol. 47, no. 1, Mar. 2020, pp. 57-65, doi:10.5798/dicletip.706005.

Vancouver

1.İlknur Çalık, Muhammet Çalık, İbrahim Hanifi Özercan, Adile Ferda Dağlı, Gökhan Artaş, Gülistan Türken, Burcu Sarıkaya. Decreased CDX2 Expression Adversely Effect On Prognosis Of Patients With Colorectal Cancer. Dicle Medical Journal. 2020 Mar. 1;47(1):57-65. doi:10.5798/dicletip.706005

Cited By

Evaluation of the Immunohistochemical Scoring System of CDX2 Expression as a Prognostic Biomarker in Colon Cancer

Diagnostics

https://doi.org/10.3390/diagnostics14101023