Epithelial‑mesenchymal transition phenotype of circulating tumor cells is associated with distant metastasis in patients with NSCLC

Abstract

Circulating tumor cells (CTCs) are closely associated with cancer metastasis in preclinical models and patients with cancer. However, to the best of the authors knowledge, it remains unknown which type of CTCs may serve the key role in cancer metastasis. The present study investigated the association between the epithelial-mesenchymal transition (EMT) phenotype of CTCs from the peripheral blood and distant metastasis in patients with non-small cell lung cancer (NSCLC). Expression of EMT markers in CTCs from a cohort of patients was detected using Canpatrol™ CTC assays. A total of 110 patients (85 patients with NSCLC and 25 patients with benign diseases) were recruited. Among the 110 patients, 88 (80.0%) were characterized as CTC positive with EMT markers. Receiver operating characteristic curves revealed that E + /M + CTCs exhibited the highest area under the curve (AUC) value of 0.876 [95% confidence interval (CI), 0.805-0.948; P<0.001) in distinguishing between patients with NSCLC and benign pulmonary diseases, and M + CTCs had the highest AUC value of 0.723 (95% CI, 0.612-0.833; P<0.001) in differentiating patients with NSCLC with distant metastasis from those with non-distant metastasis. The results indicate the potential predictive value of distant metastasis of the EMT phenotype of CTCs in the peripheral blood of patients with NSCLC.

Clinical significance of circulating tumor cells in patients with locally advanced head and neck squamous cell carcinoma

“…Tumor cells can leave the primary site, and enter vascular or lymphatic systems as CTCs to induce metastasis (37). CTCs can also return to the bone marrow reserve pool in a resting state; under certain conditions, CTCs can again enter the vascular or lymphatic systems, and travel to other organs to form distant metastases (38,39).…”

Epithelial‐to‐mesenchymal‐like transition events in melanoma

“…successful detection and isolation of CTCs using epithelial cell-surface markers (such as EpCAM and cytokeratins), seemingly conflicted with this idea [141,142]. Meanwhile, multiple isolation techniques that either employ mesenchymal markers or work label-free have confirmed the presence of key EMT markers in CTCs in a wide range of carcinomas [143][144][145][146]. In addition, so-called "hybrid CTCs", displaying mixed epithelial and mesenchymal characteristics, have also been identified [147][148][149].…”

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis

“…In agreement with the well-documented and numerous pro-metastatic functions of EMTs, the detection of certain EMT actors in CTCs has thus been correlated with poor clinical parameters such as an aggressive cancer types and a shortened OS or PFS ( Table 1 ). More particularly, CTCs harboring mesenchymal features have been reported to associate with the presence of metastases in numerous cancers including breast, lung, pancreatic, colorectal, prostate, or hepatocellular cancers [ 101 , 109 , 114 , 116 , 122 , 125 , 169 , 351 , 352 , 353 , 354 ]. Considering particular EMT/CSC molecular actors, studies, for instance, have detected CD44, often in conjunction with other canonical EMT markers, in CTCs isolated from many cancer types, which was associated with poor clinical outcomes in some studies [ 50 , 100 , 170 , 187 , 188 , 335 , 355 , 356 ].…”