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