Clinical application of detection of isolated tumor cells with cancer stem-like cells as prognostic tool in colorectal cancer patient

本研究旨在探讨结直肠癌（CRC）患者外周血（PB）、肿瘤引流静脉血（TDVB）中循环肿瘤细胞（CTC）和腹腔冲洗液中分离肿瘤细胞（ITC）的临床意义。我们选择了多种遗传标志物，包括癌相关标志物（CEA）、上皮标志物（细胞角蛋白：CK 19、CK 20）和癌干细胞样细胞标志物（CD 133）。在本研究中，Dukes'B期和C期患者中，PB或TDVB中CEA、CK和/或CD 133阳性的患者的总生存期（OS）和无病生存期（DFS）显著低于这些标志物阴性的患者。研究表明，多标志物是Dukes B期和C期癌症患者OS和DFS的重要预后因素（JCO 2011，Oncol Rep 2012）。此外，我们采用多种分子标记物CEA/CK/CD 133检测结直肠癌患者根治性切除术后腹腔冲洗液中ITC的预后价值。在本研究中，CEA、CK和/或CD 133 mRNA阳性患者的OS和腹膜无复发生存率显著低于标记基因阴性患者。研究表明，腹膜冲洗液中的CEA、CK和CD 133 mRNA是OS和DFS的独立预后因素（Oncology 2010）。

In this study, we aimed to clarify a clinical significance of circulating tumor cell(CTC) in peripheral blood(PB) and tumor drainage vein blood(TDVB), and isolated tumor cells(ITC) in peritoneal washings of colorectal cancer(CRC) patients. We selected the multiple genetic marker include the cancer associate marker(CEA), epithelial markers(cytokeratin : CK19, CK20), and cancer stem cell-like cell marker(CD133). In this study, overall survival(OS) and disease-free survival(DFS) of Dukes' stage B and C patients who were positive for CEA, CK and/or CD133 in PB or TDVB were significantly worse than those of patients who were negative for these markers. It was demonstrated that multimarker was a significant prognostic factor for OS and DFS in patients with Dukes stage B and C cancer(JCO 2011, Oncol Rep 2012). Furthermore, we examined the prognostic value of ITC in peritoneal washings from CRC patients after curative resection using multiple molecular markers CEA/CK/CD133.In this study, OS and peritoneal recurrence-free survival rates in CEA, CK and/or CD133 mRNA-positive patients were significantly lower than those of marker gene-negative patients. It was demonstrated that CEA, CK and CD133 mRNAs in peritoneal washings were independent prognostic factors for OS and DFS(Oncology 2010).