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.

Clinical value of circulating tumor cells and hematological parameters in 617 Chinese patients with colorectal cancer: Retrospective analysis

“…In this study, CTCs value increased with the deepening of tumor invasion depth, distant organ metastasis, and the progression of TNM staging (P < 0.05), but was not correlated with lymph node metastasis (P > 0.05). This is consistent with the study of Zhong et al [10], which showed that CTCs can well predict the depth of colorectal cancer invasion, the possibility of metastasis formation in the distal organ, and tumor staging.…”

Small bowel adenocarcinoma in neoterminal ileum in setting of stricturing Crohn’s disease: A case report and review of literature

“…Recent work describes the merits of this method in the detection and real time monitoring of CRC, allowing repeated temporal sampling for detection at curable stages[ 24 - 26 ]. A study done by Zhong et al [ 27 ] found that mesenchymal cell marker vimentin (M-CTC) in liquid biopsy directly correlated with tumor size, tumor, node and metastasis stage and vascular invasion. Unfortunately, the cost of liquid biopsy[ 26 ] outweighs its feasibility as a screening method, warranting discovery of affordable techniques that serve the same purpose for SBA.…”

Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer

“…They showed that tumor metastasis is more significantly associated with the presence of M-CTCs and CTMs than with other CTC subgroups [ 39 ]. Similarly, Yuchen Zhong et al demonstrated that M-CTCs were correlated with tumor size, T stage, TNM stage, vascular invasion, and CEA, and M-CTCs > 1 were discovered to be associated with worse DFS [ 40 ]. According to a publication-based meta-analysis published in 2018 that included 15 published investigations with a total of 3129 patients, the presence of CTCs was highly correlated with poor survival (OS: HR = 2.36, 95% CI: 1.87–2.97; P = 0.006) and aggressive disease progression (PFS: HR = 1.83, 95% CI: 1.42–2.36; P < 0.00001).…”