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Pretreatment detection of circulating and tissue CD133CD44+ cancer stem cells as a prognostic factor affecting the outcomes in Egyptian patients with colorectal cancer

Authors Zahran AM, Amal Rayan, Fakhry H, Attia AM, Ashmawy AM, Soliman A, Elkady A, Hetta HF

Received 3 October 2018

Accepted for publication 27 December 2018

Published 7 February 2019 Volume 2019:11 Pages 1237—1248

DOI https://doi.org/10.2147/CMAR.S189653

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Asmaa M Zahran,1 Amal Rayan,2 Hussein Fakhry,3 Alia M Attia,4 Ahmed M Ashmawy,5 Ahmed Soliman,6 Azza Elkady,7 Helal F Hetta8,9

1Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt; 2Department of Clinical Oncology, Assiut University Hospital, Assiut University, Assiut, Egypt; 3Department of Surgical Oncology, South Egypt Cancer Institute, Assiut, Egypt; 4Department of Radiation Oncology, South Egypt Cancer Institute, Assiut, Egypt; 5Department of Internal Medicine, Assiut University Hospital, Assiut, Egypt; 6Department of General Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt; 7Sohag University Medical Administration, Sohag, Egypt; 8Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 9Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Background and aim: Colorectal cancer is one of the most common malignant tumors worldwide. As CD133 and CD44 are notable markers of cancer stem cells (CSCs) identity, it is thought to be a predictive indicator for colorectal cancer. The aim of this study was to investigate the cell cycle state of CD133+ CD44+ and CD133 CD44cells, isolated from primary human colorectal tumors, and to assess the clinical impact of CD133+ CD44+ CSCs on patients’ outcome regarding disease-free survival (DFS) and overall survival (OS).
Materials and methods: Tissue samples were collected from 50 primary colorectal cancer patients. Flow cytometric analysis was performed to isolate tissue CD133+ CD44+ CSCs and CD133 CD44 tumor cells from primary colorectal cancer tissue to compare the cell cycle of both types of cells. Also circulating CSCs were assessed by flow cytometry.
Results: Higher percentage of tissue CD133+ CD44+ CSCs isolated from colorectal cancer patients was found in G0/G1 phase. However, tissue CD133 CD44 tumor cells were predominantly found in the S phase; there were significant negative correlations between tissue CD133+ CD44+ CSCs and DFS and OS (r=−0.470, P<0.001, respectively and r=−0.487, P<0.001, respectively), also significant negative correlations between tissue CSCs and DFS and OS (r=−0.548, P<0.001, respectively and r=−0.497, P<0.001, respectively). Only the pathological grade (P<0.004) and T stage (P<0.004) had a significant effect on circulating CSC counts.
Conclusion: Tissue CD133+ CD44+ CSCs were more quiescent than tissue CD133 CD44 tumor cells and both circulating CSCs and tissue CSCs were considered independent negative prognostic factors on OS and DFS.

Keywords: cancer stem cells, colorectal cancer, CD133+ CD44+

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