Published online Jan 7, 2019. doi: 10.3748/wjg.v25.i1.138
Peer-review started: October 15, 2018
First decision: November 7, 2018
Revised: December 5, 2018
Accepted: December 6, 2018
Article in press: December 6, 2018
Published online: January 7, 2019
Circulating tumor cells (CTCs) have been demonstrated to be a prognostic indicator in numerous cancers. However, in pancreatic ductal adenocarcinoma (PDAC), CTCs remain to be studied. Here, we report for the first time the prognostic utility of CTCs, as detected by CanPatrol CTC enrichment technique, in patients with PDAC. Our data support the potential clinical value of PDAC CTCs. Both total CTC number and CTC epithelial-to-mesenchymal transition (EMT) phenotype may act as potential biomarkers for PDAC prognosis.
In the present study, we explored the relationships between clinicopathological parameters and the relative abundance of three circulating EMT-CTC subpopulations. We found that CTC status correlated with lymph node metastasis, TNM stage, distant metastasis, blood lymphocyte counts, and the neutrophil-to-lymphocyte ratio (NLR). Kaplan-Meier survival analysis showed that patients with ≥ 6 total CTCs had significantly decreased OS and PFS compared to patients with < 6 total CTCs. The presence of M-CTCs was positively correlated with TNM stage and distant metastasis. Additionally, lymphocyte counts and NLR in patients without CTCs were significantly different from those in patients testing positive for each CTC subpopulation. Our data support the potential clinical value of PDAC CTCs. Furthermore, our data also provide support for further large well-designed clinical trials to explore CTC counts as indicators of PDAC progression.
The objective of this research was to explore the relationships between clinicopathological parameters and the relative abundance of the three circulating EMT-CTC subpopulations in PDAC. This research demonstrated that positive CTC status was significantly correlated with lymph node metastasis, distant metastasis, late TNM stage, and poor patient prognosis. Meanwhile, M-CTCs were most common in patients with advanced cancer. These results demonstrated that classifying CTCs by EMT markers helps to identify the more aggressive CTC subpopulations and provides useful evidence for determining a suitable clinical approach.
This research utilized the cell size- and phenotype-based CanPatrol CTC filtration system to isolate CTCs. CTC subpopulations were identified using a multiplex RNA-ISH assay. Four epithelial biomarkers (epithelial cell adhesion molecule and cytokeratin 8/18/19), two mesenchymal biomarkers (vimentin and twist), and a leukocyte biomarker, CD45, were applied to capture and characterize the CTCs.
This research indicated that the presence of CTCs was significantly associated with PDAC poor prognosis. Moreover, M-CTCs were most common in patients with advanced cancer. These results demonstrate that CTCs are promising biomarker for PDAC prognosis and identification of EMT markers in CTCs provide more information on tumor progression.
In the present study, a novel technology called CanPatrol CTC filtration system applying a combination of epithelial and mesenchymal markers was used to detect CTCs in peripheral blood from 107 patients with PDAC. We found that CTC positivity was correlated with clinicopathologic variables and outcomes. Meanwhile, the presence M-CTCs was associated with advanced stage and distant metastasis. These results demonstrate that CTC enumeration and classification show promise as a prognostic biomarker and may provide useful evidence for determining a suitable clinical approach.
This research supports the potential clinical value of PDAC CTCs. Both total CTC number and CTC EMT phenotype may act as potential biomarkers for PDAC prognosis. However, our study suffered from a small sample size, and the results should be interpreted with caution. Large well-designed clinical trials are required to elucidate the potential value of EMT markers in CTCs.