Role of Phenotypes of Circulating Tumor Cells in the Diagnosis and Treatment of Colorectal Cancer

Abstract

Objective

To investigate the relationship between circulating tumor cells (CTCs) and their subpopulations and colorectal cancer (CRC). To explore the application of CTCs’ numbers and positive rates in the diagnosis and treatment of CRC, and to assess the effect of surgery on CTCs numbers and positivity.

Methods

We identified CTCs using the CanPatrol technique after enrollment. Peripheral blood samples were collected from 74 CRC patients before anti-tumor treatment. CTCs can be divided into the following three phenotypes: epithelial CTCs (E-CTCs) (EpCAM+, Vimentin-), mesenchymal CTCs (M-CTCs) (EpCAM-, Vimentin+), and mixed CTCs (E/M-CTCs) (EpCAM+, Vimentin+). CTCs and the proportion of subtypes were statistically compared with clinicopathological characteristics.

Results

The positive rate of M-CTCs was significantly higher in patients with tumor size ≥5 cm (85.7% vs 49.1%, P = 0.004) and carcinoembryonic antigen (CEA) >5 ng/mL (83.3% vs 51.0% p = 0.024). Moreover, the T stage (T1 0, T2 33.3%, T3 59.4%, T4 100%, p < 0.0005) and TNM stage (stage I 11.8%, stage II 79.2%, stage III 64.3%, stage IV 100%, p < 0.0005) were correlated with the positive rate of M-CTCs. We also found that the proportion of M-CTCs was correlated with the T stage (p < 0.0005) and TNM stage (p=0.0200), but not with the N stage (p=0.6889). In survival analysis, M-CTCs >1 were found associated with worse disease-free survival (p=0.007). After treatment, the number and proportion of CTCs and M-CTCs were significantly reduced.

Conclusion

The positive rate of M-CTCs was associated with tumor size, T stage, TNM stage, vascular invasion, and CEA. As the disease progressed, the proportion of M-CTCs gradually increased, and the survival performance was worse in patients with a high positive rate of M-CTCs.

Keywords:

• circulating tumor cells
• colorectal cancer
• surgery
• EMT

Acknowledgments

This research was supported by the [National Natural Science Foundation of China Grant number: 81872034], [Natural Science Foundation of Heilongjiang Province of China Grant number: H2017016], and [Wu Jieping Medical Foundation Grant number: 320.6750.15183].

Disclosure

The authors report no conflicts of interest in this work.