Abstract
Background
Colorectal carcinoma (CRC) is the third most common human cancer. Twist, a basic helix-loop-helix (bHLH) transcription factor, is an epithelial-mesenchymal transition ((EMT) inducer that has been involved in carcinogenesis and chemoresistance. Also, the enhancer of Zeste homolologue2 (EZH2), a member of the polycomb group of genes, had been associated with poor prognosis in several malignancies.
Objective
To evaluate the expression of Twist1 and EZH2 in colon carcinoma in Egyptian patients and its relation to clinicopathological parameters, prognosis, and survival.
Methods
Twist1 and EZH2 expressions were evaluated immunohistochemically in 50 cases of colorectal tumors (12 colon adenomas and 38 colon carcinomas) and 20 samples from normal colonic mucosa.
Results
The expression of Twist1 and EZH2 was significantly higher in colon adenoma and carcinoma than that in normal colonic mucosa (P < 0.05). Twist1 and EZH2 expressions were associated with decreased tumor differentiation, advanced stage, and lymph node metastasis. Twist1 and EZH2 expressions were significantly related to 3-year disease-free survival (P = 0.005 and 0.002 respectively) and 3-year overall survival (P = 0.045 and 0.039, respectively).
Conclusions
Twist1 and EZH2 may serve as prognostic predictors for colon carcinoma and may have a potential role as therapeutic targets in patients with colon carcinoma in the future.
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References
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(12):2893–917.
Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–93.
Metwally IS, Shetiwy M, Elalfy AF, et al. Epidemiology and survival of colon cancer among Egyptians: a retrospective study. J Coloproctol (Rio J). 2018;38(1):24–9.
Zhu D, Chen X, Zhang W, Wang JZ, Ouyang MZ, Zhong Q, et al. Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance. Am J Cancer Res. 2015;5(6):2000–11.
Gomez I, Peña C, Herrera M, et al. TWIST1 is expressed in colorectal carcinomas and predicts patient Survival. PLoS One. 2011;6(3):18023.
Segovia C, Paramio J, Martínez-Fernández M. Epigenetic mutations and cancer therapy effective (EZH2). Transl Cancer Res. 2017;6:629–34.
Bachmann I, Halvorsen O, Collett K, Stefansson IM, Straume O, Haukaas SA, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol. 2006;24:268–73.
Cakouros D, Isenmann S, Cooper L, Zannettino A, Anderson P, Glackin C, et al. Twist-1 induces Ezh2 recruitment regulating histone methylation along the Ink4A/Arf locus in mesenchymal stem cells. Mol Cell Biol. 2012;32(8):1433–41.
Zhang Q, Dong P, Liu X, et al. Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis. Sci Rep. 2017;7:6804.
Byrd DR, et al. In: Edge SB, editor. AJCC cancer staging manual. Vol. 649. New York: Springer; 2010.
Kim KH, Kim L, Choi SJ, Han JY, Kim JM, Chu YC, et al. The clinicopathological significance of epithelial-mesenchymal transition associated protein expression in head and neck squamous cell carcinoma. Korean J Pathol. 2014;48(4):263–9.
Lamouille S, Xu J, Derynck R, et al. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15:178–96.
Li S, Kendall SE, Raices R, et al. TWIST1 associates with NF-kappaB subunit RELA via carboxyl-terminal WR domain to promote cell-autonomous invasion through IL8 production. BMC Biol. 2012;10:73.
Niu X, Zhang T, Liao L, Zhou L, Lindner DJ, Zhou M, et al. The von Hippel Lindau tumor suppressor protein regulates gene expression and tumor growth through histone demethylase JARID1C. Oncogene. 2012;31:776–86.
Chou RH, Yu YL, Hung MC. The roles of EZH2 in cell lineage commitment. Am J Transl Res. 2011;3:243–50.
McCabe M, Creasy C. EZH2 as a potential target for cancer therapy. Epigenomics. 2014;6(3):341–51.
Hong R, Lim S. Overexpression of Twist in colorectal adenocarcinoma. Basic Appl Pathol. 2009;2(1):15–20.
Kim Y, Kim G, Kown C, et al. TWIST1 and SNAL1 as markers of poor prognosis in human colorectal cancer are associated with the expression of ALDH1 and TGF-β1. Oncol Rep. 2014;31(3):1380–8.
Yusup A, Huji B, Fang C, Wang F, Dadihan T, Wang HJ, et al. Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis. World J Gastroenterol. 2017;23(1):110–20.
Kroepil F, Fluegen G, Totikov Z, et al. Downregulation of CDH1 is associated with the expression of SNAIL1 in colorectal adenomas. PLoS One. 2012;7(9):e46665.
El Naby A, Mohammed S, et al. Immunohistochemical expression of Twist in colorectal carcinoma. Menoufia Med J. 2015;28.3:725.
Galván J, Helbling M, Koelzer V, Tschan MP, Berger MD, Hädrich M, et al. TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenomenon. Oncotarget. 2015;6(2):874–8.
Valdés-Mora F, Del Pulgar TG, Bandrés E, et al. TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectal cancer. Ann Surg Oncol. 2009;16(1):78–87.
Ohuchi M, Sakamoto Y, Tokunaga R, Kiyozumi Y, Nakamura K, Izumi D, et al. Increased EZH2 expression during the adenoma-carcinoma sequence in colorectal cancer. Oncol Lett. 2018;16(4):5275–81.
Kurihara H, Maruyama R, Ishiguro K, Kanno S, Yamamoto I, Ishigami K, et al. The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway. Oncotarget. 2016;7(11):12704–17.
Fussbroich B, Wagener N, Macher-Geoppinger S, et al. EZH2 depletion blocks the proliferation of colon cancer cells. PLoS One. 2011;6(7):e21651.
Kuroki H, Hayashi H, Okabe H, Hashimoto D, Takamori H, Nakahara O, et al. EZH2is associated with malignant behavior in pancreatic IPMN via p27kip1 downregulation. PLoS One. 2014;9(8):e100904.
Liu X, Liu H, Gu I, et al. EZH2 Expression and its correlation with clinicopathological features in patients with colorectal carcinoma. OpenLlife Sci. 2016;11(1):287–92.
Chen Z, Yang P, Li W, et al. Expression of EZH2 is associated with poor outcome in colorectal cancer. Oncol Lett. 2018;15(3):2953–61.
Wang CG, Ye YJ, Yan J, et al. EZH2, and STAT6 expression profiles are correlated with colorectal cancer stage and prognosis. World J Gastroenterol. 2010;16:2421–7.
Kodach LL, Jacobs KR, Heijimans J, et al. The role of EZH2 and DNA methylation in the silencing of the tumour suppressor RUNX3 in colorectal cancer. Carcinogenesis. 2010;31:1567–75.
Lin YW, Ren LL, Xiong H, du W, Yu YN, Sun TT, et al. Role of STAT3 and vitamin D receptor in EZH2-mediated invasion of human colorectal cancer. J Pathol. 2013;230:277–90.
Takawa M, Masoda K, Kunizaki M, et al. Validation of the histone methyltransferase EZH2 as a therapeutic target for various types of human cancer and as a prognostic marker. Cancer Sci. 2011;102:1298–305.
Mahmoud, Abla S., and Dina A. Khairy. Clinicopathological Significances of EZH2 & Twist-1 combined expressions in renal cell carcinoma (RCC). Med. J. Cairo Univ. 2018;86(4):2019-28.
Abdelrahman A, Arafa S, Ragab A. Prognostic value of Twist-1, E-cadherin, and EZH2 in prostate cancer: an immunohistochemical study. Turkish J Pathol. 2017;33:198–210.
Acknowledgments
We thank all our colleagues in the Pathology, Clinical Oncology, General Surgery, and Internal Medicine Departments, Faculty of Medicine, Zagazig University, for their support and encouragement.
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Abdel Raouf, S.M., Ibrahim, T.R., Abdelaziz, L.A. et al. Prognostic Value of TWIST1 and EZH2 Expression in Colon Cancer. J Gastrointest Canc 52, 90–98 (2021). https://doi.org/10.1007/s12029-019-00344-4
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DOI: https://doi.org/10.1007/s12029-019-00344-4