Clinical Significance of Disseminated Pluripotent Tumor Cell Signature Expression in the Bone Marrow from Patients with Colorectal Cancer.

Purpose: Disseminated tumor cells (DTCs) are critically involved in tumor relapse and survival in several invasive tumors. We previously showed that the ATP-binding cassette (ABC) transporter, , is a chemoresistance mediator expressed on specific cell subsets in colorectal cancer (CRC) and other malignancies. This study evaluated the molecular signature expression and its clinical relevance of DTCs in bone marrow from patients with colon cancer.

Methods: This study included 49 consecutive patients (UICC stage I-IV) that underwent curatively intended or palliative surgery for CRC. We analyzed cells from bone marrow aspirates obtained before surgery and derived from patients that had completed minimally a 5-year follow-up. The gene expression of in comparison to (molecule for identifying cancer initiating cells), (an intestinal stem cell marker) as well as Cytokeratin (CK) 20 (terminally differentiated tumor cells of epithelial origin) in these cells was evaluated.

Results: Bone marrow analysis showed differential expression between the analyzed genes. and and to lesser extent and genes were significantly expressed in the analyzed cells from bone marrow aspirates while only and were significantly negative associated with tumor progress and overall survival.

Conclusion: Overexpression of and in bone marrow negatively influenced patient survival pointing to a specific chemo resistant and pluripotent cell subgroup of DTCs in the bone marrow. like positive cells seem to be involved in limited tumor related patient survival, suggesting that and -positive cells may be relevant for specific clinical intervention strategies.