Pretreatment detection of circulating and tissue CD133+ CD44+ cancer stem cells as a prognostic factor affecting the outcomes in Egyptian patients with colorectal cancer

Asmaa M Zahran; Amal Rayan; Hussein Fakhry; Alia M Attia; Ahmed M Ashmawy; Ahmed Soliman; Azza Elkady; Helal F Hetta

doi:10.2147/CMAR.S189653

Pretreatment detection of circulating and tissue CD133⁺ CD44⁺ cancer stem cells as a prognostic factor affecting the outcomes in Egyptian patients with colorectal cancer

Cancer Manag Res. 2019 Feb 7:11:1237-1248. doi: 10.2147/CMAR.S189653. eCollection 2019.

Authors

Asmaa M Zahran¹, Amal Rayan², Hussein Fakhry³, Alia M Attia⁴, Ahmed M Ashmawy⁵, Ahmed Soliman⁶, Azza Elkady⁷, Helal F Hetta^{8

9}

Affiliations

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

Abstract

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^- CD44^-cells, 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: CD133+ CD44+; cancer stem cells; colorectal cancer.