Epithelial-mesenchymal transition classification of circulating tumor cells predicts clinical outcomes in progressive nasopharyngeal carcinoma

Abstract

BackgroundLiquid biopsy facilitates the enrichment and isolation of circulating tumor cells (CTCs) in various human cancers, including nasopharyngeal carcinoma (NPC). Characterizing CTCs allows observation of the evolutionary process of single tumor cells undergoing blood-borne dissemination, such as epithelial-mesenchymal transition. However, the prognostic value of phenotypic classification of CTCs in predicting the clinical outcomes of NPC remains poorly understood.Patients and methodsA total of 92 patients who met the inclusion criteria were enrolled in the present study. The CanPatrol™ CTC technology platform was employed to isolate CTCs, and an RNA in situ hybridization-based system was used for phenotypic classification. Kaplan–Meier survival curves were used for univariate survival analysis, and the log-rank test was performed for between-group comparisons of the survival curves.ResultsCTCs were detected in 88.0% (81/92) of the enrolled patients with NPC. The total CTC number did not vary between the T and N stages or between Epstein–Barr virus DNA-positive and -negative cases. The numbers of total CTCs and epithelial/mesenchymal (E/M) hybrid CTCs decreased significantly at 3 months post concurrent chemoradiotherapy (P=0.008 and P=0.023, respectively), whereas the numbers of epithelial or mesenchymal CTCs did not decrease. E/M hybrid-predominant cases had lower disease-free survival (P=0.043) and distant metastasis-free survival (P=0.046) rates than non-E/M hybrid-predominant cases.ConclusionCTC classification enables a better understanding of the cellular phenotypic alterations responsible for locoregional invasion and distant metastasis in NPC. E/M hybrid-predominant CTC distribution predicts unfavorable clinical outcomes in patients with progressive NPC.

Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem

“…Our previous study indicated that dissociated NPC cells in the circulation exhibiting EMT/CSCs features were endowed with their metastatic potentials 61 . CTCs can be used for tumor stage determination and prognosis prediction of NPC at all stages, and especially epithelial/mesenchymal (E/M) hybrid CTCs predict adverse outcomes 110 , 111 . To be more exhilarating, a study showed that CTCs can be a novel more sensitive biomarker for minimal residual disease (MRD) of NPC patients 112 .…”

Prognostic Significance of Excision Repair Cross-Complementation Group 1 on Circulating Tumor Cells for Nasopharyngeal Carcinoma

“… 23 This may be due to the acquisition of mesenchymal properties by tumor cells through EMT, which includes characteristics such as loss of cell polarity, reduced cell adhesion, induced cell migration, and increased intravascular permeability, significantly contributes to the progression and metastasis of malignant tumors. 29 , 30 Remarkably, mesenchymal-type CTCs exhibit enhanced invasiveness due to their acquisition of mesenchymal phenotypic traits. 30 , 31 …”

“… 29 , 30 Remarkably, mesenchymal-type CTCs exhibit enhanced invasiveness due to their acquisition of mesenchymal phenotypic traits. 30 , 31 …”

Circulating tumor cells (CTCs) and hTERT gene expression in CTCs for radiotherapy effect with lung cancer

“…The CanPatrol™ CTC enrichment technique (SurExam, Guangzhou, China) was performed on peripheral blood samples to isolate and classify CTCs as previously described [ 10 , 11 ]. A 5-mL peripheral blood sample was collected using EDTA-anticoagulated blood collection tubes and mixed upside down.…”

“…The CanPatrol™ assay system (SurExam, Guangzhou, China) [ 10 , 11 ] is a second-generation CTC enrichment technology based on immuno-removal combined with nano-filtration. It does not rely on specific antibody capture and has a removal efficiency of > 99.97% for leukocytes and a recovery rate of > 80% for tumor cells.…”