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

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