Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with dukes' stage B and C colorectal cancer

Hisae Iinuma, Toshiaki Watanabe, Koshi Mimori, Miki Adachi, Naoko Hayashi, Junko Tamura, Keiji Matsuda, Ryoji Fukushima, Kota Okinaga, Mitsuru Sasako, Masaki Mori

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Abstract

Purpose Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery. Patients and Methods In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n=420) or prospective validation set (n=315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay. Results In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95% CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95% CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer. Conclusion In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.

Original languageEnglish
Pages (from-to)1547-1555
Number of pages9
JournalJournal of Clinical Oncology
Volume29
Issue number12
DOIs
Publication statusPublished - Apr 20 2011

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Circulating Neoplastic Cells
Neoplastic Stem Cells
Colorectal Neoplasms
Recurrence
Carcinoembryonic Antigen
Keratins
Disease-Free Survival
Survival
Keratin-19
Neoplasms
Messenger RNA
Adjuvant Chemotherapy
Genetic Markers
Reverse Transcription

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with dukes' stage B and C colorectal cancer. / Iinuma, Hisae; Watanabe, Toshiaki; Mimori, Koshi; Adachi, Miki; Hayashi, Naoko; Tamura, Junko; Matsuda, Keiji; Fukushima, Ryoji; Okinaga, Kota; Sasako, Mitsuru; Mori, Masaki.

In: Journal of Clinical Oncology, Vol. 29, No. 12, 20.04.2011, p. 1547-1555.

Research output: Contribution to journalArticle

Iinuma, Hisae ; Watanabe, Toshiaki ; Mimori, Koshi ; Adachi, Miki ; Hayashi, Naoko ; Tamura, Junko ; Matsuda, Keiji ; Fukushima, Ryoji ; Okinaga, Kota ; Sasako, Mitsuru ; Mori, Masaki. / Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with dukes' stage B and C colorectal cancer. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 12. pp. 1547-1555.
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title = "Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with dukes' stage B and C colorectal cancer",
abstract = "Purpose Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery. Patients and Methods In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n=420) or prospective validation set (n=315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay. Results In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95{\%} CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95{\%} CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer. Conclusion In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.",
author = "Hisae Iinuma and Toshiaki Watanabe and Koshi Mimori and Miki Adachi and Naoko Hayashi and Junko Tamura and Keiji Matsuda and Ryoji Fukushima and Kota Okinaga and Mitsuru Sasako and Masaki Mori",
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T1 - Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with dukes' stage B and C colorectal cancer

AU - Iinuma, Hisae

AU - Watanabe, Toshiaki

AU - Mimori, Koshi

AU - Adachi, Miki

AU - Hayashi, Naoko

AU - Tamura, Junko

AU - Matsuda, Keiji

AU - Fukushima, Ryoji

AU - Okinaga, Kota

AU - Sasako, Mitsuru

AU - Mori, Masaki

PY - 2011/4/20

Y1 - 2011/4/20

N2 - Purpose Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery. Patients and Methods In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n=420) or prospective validation set (n=315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay. Results In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95% CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95% CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer. Conclusion In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.

AB - Purpose Using multiple genetic markers, including cancer stem-like cells, we evaluated the clinical significance of circulating tumor cells (CTCs) as a prognostic factor for overall survival (OS) and disease-free survival (DFS) in the peripheral blood (PB) of patients with colorectal cancer (CRC) who had undergone curative surgery. Patients and Methods In a multi-institutional study, 735 patients with CRC were assigned to a retrospective training set (n=420) or prospective validation set (n=315). CTCs that expressed carcinoembryonic antigen (CEA), cytokeratin (CK) 19, CK20, and/or CD133 (CEA/CK/CD133) mRNA in PB were detected using real-time reverse transcription polymerase chain reaction assay. Results In the training sets, OS and DFS of patients who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .001). At each staging analysis, OS and DFS of patients with Dukes' stage B or C cancer who were positive for CEA/CK/CD133 were significantly worse than those of patients who were negative for these markers (P < .003 and P < .001 in Dukes' stage B; P < .001 in Dukes' stage C). In contrast, in patients with Dukes' stage A, no significant differences were seen between patients who were positive for these markers and those who were negative. Cox multivariate analysis demonstrated that CEA/CK/CD133 was a significant prognostic factor for OS (hazard ratio [HR], 3.84; 95% CI, 2.41 to 6.22; P < .001) and DFS (HR, 3.02; 95% CI, 1.83 to 5.00; P < .001). In particular, in patients with Dukes' stage B and C cancer, CEA/CK/CD133 demonstrated significant prognostic value. In validation sets, similar results were confirmed in patients with Dukes' stage B and C cancer. Conclusion In patients with Dukes' stage B and C CRC who require adjuvant chemotherapy, detection of CEA/CK/CD133 mRNA in PB is a useful tool for determining which patients are at high risk for recurrence and poor prognosis.

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