Clinical Significance of Disseminated Pluripotent Tumor Cell Signature Expression in the Bone Marrow from Patients with Colorectal Cancer.
Clinical Significance of Disseminated Pluripotent Tumor Cell Signature Expression in the Bone Marrow from Patients with Colorectal Cancer.
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DOI：
10.4172/1948-5956.1000490
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Waaga-Gasser AM
中科院分区：
文献类型：
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作者：
Gasser M;Kim M;Rehder R;Frank N;Frank M;Grimmig T;Moench R;Ribas C;Illert B;Germer CT;Rosenwald A;Waaga-Gasser AM
播散性肿瘤细胞（DTC）在几种侵袭性肿瘤中与肿瘤复发和存活密切相关。我们以前表明，ATP结合盒（ABC）转运蛋白，ABCB 5，是一种化学耐药性介导剂表达的特定细胞亚群在结直肠癌（CRC）和其他恶性肿瘤。本研究评估了结肠癌患者骨髓中DTC的分子特征表达及其临床相关性。本研究纳入了49例连续患者（UICC I-IV期），这些患者接受了预期治愈性或姑息性CRC手术。我们分析了手术前获得的骨髓穿刺液中的细胞，这些细胞来自至少完成了5年随访的患者。评估了ABCB 5与CD 133（用于鉴定癌症起始细胞的分子）、Lgr 5（肠干细胞标志物）以及细胞角蛋白（CK）20（上皮来源的终末分化肿瘤细胞）在这些细胞中的基因表达。骨髓分析显示所分析的基因之间的差异表达。ABCB 5和Lgr 5以及较小程度的CD 133和CK 20基因在来自骨髓抽吸物的分析细胞中显著表达，而只有ABCB 5和Lgr 5与肿瘤进展和总生存率显著负相关。ABCB 5和Lgr 5在骨髓中的过表达对患者的存活率产生负面影响，这表明骨髓中存在特定的化疗耐药和多能细胞亚群的DTC。ABCB 5样Lgr 5阳性细胞似乎参与有限的肿瘤相关患者存活，表明ABCB 5和Lgr 5阳性细胞可能与特定的临床干预策略相关
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, ABCB5, 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. 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 ABCB5 in comparison to CD133 (molecule for identifying cancer initiating cells), Lgr5 (an intestinal stem cell marker) as well as Cytokeratin (CK) 20 (terminally differentiated tumor cells of epithelial origin) in these cells was evaluated. Bone marrow analysis showed differential expression between the analyzed genes. ABCB5 and Lgr5 and to lesser extent CD133 and CK20 genes were significantly expressed in the analyzed cells from bone marrow aspirates while only ABCB5 and Lgr5 were significantly negative associated with tumor progress and overall survival. Overexpression of ABCB5 and Lgr5 in bone marrow negatively influenced patient survival pointing to a specific chemo resistant and pluripotent cell subgroup of DTCs in the bone marrow. ABCB5 like Lgr5 positive cells seem to be involved in limited tumor related patient survival, suggesting that ABCB5- and Lgr5-positive cells may be relevant for specific clinical intervention strategies