Prognostic significance of CTCs and CSCs of tumor drainage vein blood in Dukes' stage B and C colorectal cancer patients

Abstract

The clinical significance of circulating tumor cells (CTCs) including cancer stem cells (CSCs) (CTC/CSC) in the tumor drainage vein blood of patients with colorectal cancer (CRC) is unclear. In this study, we investigated the prognostic value of CTC/CSC that express carcinoembryonic antigen (CEA) cytokeratin 19 (CK19), CK20 and/or CD133 (CEA/CK/CD133) mRNA in the tumor drainage blood of CRC patients with Dukes' stage B and C. We examined tumor drainage blood from 197 patients with Dukes' stage B and C CRC. CTCs that expressed CEA, CK19, CK20 and CD133 mRNA were detected using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Each mRNA level was normalized with GAPDH mRNA levels. In the relationship between the expression of CEA/CK/CD133 in the tumor drainage blood and clinicopathological factors, a significant correlation was observed between CEA/CK/CD133 expression and Dukes' stage (p<0.041). In CRC patients with Dukes' stage B and C, disease-free (DFS) and overall survival (OS) of patients with CEA/CK/CD133 positive in the tumor drainage blood were significantly worse than that of marker gene negative patients. In contrast, in patients with Dukes' stage A, no significant differences were shown between these groups. By Cox progression analysis, it was shown that CEA/CK/CD133 mRNA in tumor drainage blood was an independent prognostic factor for DFS and OS in patients with Dukes' stage B and C. These results suggest that detecting CEA/CK/CD133 mRNA in tumor drainage blood by the real-time RT-PCR method would have a prognostic value in CRC patients with Dukes' stage B and C.

Figure 1

Kaplan-Meier survival curves for OS and DFS and status of CEA/CK/CD133 positivity in patients with Dukes' stage B cancer. Significant differences were shown between the CEA/CK/CD133 positive (+) and negative group (−). ^*P-value<0.05.

Figure 2

Kaplan-Meier survival curves for OS and DFS and status of CEA/CK/CD133 positivity in patients with Dukes' stage C cancer. Significant differences were shown between the CEA/CK/CD133 positive (+) and negative group (−). ^*P-value<0.05.

Figure 3

Kaplan-Meier survival curves for OS and DFS and status of CEA/CK positivity in patients with Dukes' stage B cancer. Significant differences were not seen between the CEA/CK positive (+) and negative group (−).

Figure 4

Kaplan-Meier survival curves for OS and DFS and status of CD133 positivity in patients with Dukes' stage B cancer. Significant differences were not seen between the CD133 positive (+) and negative group (−).

Figure 5

Kaplan-Meier survival curves for OS and DFS and status of CEA/CK positivity in patients with Dukes' stage C cancer. Significant differences were shown between the CEA/CK positive (+) and negative group (−). ^*P-value<0.05.

Figure 6

Kaplan-Meier survival curves for OS and DFS and status of CD133 positivity in patients with Dukes' stage C cancer. Significant differences were not seen between the CD133 positive (+) and negative group (−).