Epithelial–mesenchymal transition markers expressed in circulating tumor cells in hepatocellular carcinoma patients with different stages of disease

Abstract We aimed to determine prognosis value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in epithelial ovarian cancer(EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among training group(n=114) and validation group(n=38). By regression screening, both CTC counts(HR 1.187; 95%CI 1.098-1.752; p=0.012) and M-CTC(HR 1.098; 95%CI 1.047-1.320; p=0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive value for nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107) and the nomogram(p=0.0021) were drawn with significant difference. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016

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Heterogeneity in Circulating Tumor Cells: The Relevance of the Stem-Cell Subset

Cancers ◽

10.3390/cancers11040483 ◽

2019 ◽

Vol 11 (4) ◽

pp. 483 ◽

Cited By ~ 37

Author(s):

Chiara Agnoletto ◽

Fabio Corrà ◽

Linda Minotti ◽

Federica Baldassari ◽

Francesca Crudele ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Epithelial Mesenchymal Transition ◽

Cell Subset ◽

Intermediate Phenotype ◽

Current Evidence ◽

Early Event ◽

Tumor Type ◽

Mesenchymal Transition ◽

Immunodeficient Mice

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial–mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity.

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