Abstract
Gastrointestinal (GI) cancers constitute a group of highest morbidity worldwide, with colorectal cancer (CRC) and gastric cancer being among the most frequently diagnosed. The majority of gastrointestinal cancer patients already present metastasis by the time of diagnosis, which is widely associated with cancer-related death. Accumulating evidence suggests that epithelial-to-mesenchymal transition (EMT) in cancer promotes circulating tumor cell (CTCs) formation, which ultimately drives metastasis development. These cells have emerged as a fundamental tool for cancer diagnosis and monitoring, as they reflect tumor heterogeneity and the clonal evolution of cancer in real-time. In particular, EMT phenotypes are commonly associated with therapy resistance. Thus, capturing these CTCs is expected to reveal important clinical information. However, currently available CTC isolation approaches are suboptimal and are often targeted to capture epithelial CTCs, leading to the loss of EMT or mesenchymal CTCs. Here, we describe size-based CTCs isolation using the RUBYchip™, a label-free microfluidic device, aiming to detect EMT biomarkers in CTCs from whole blood samples of GI cancer patients. We found that, for most cases, the mesenchymal phenotype was predominant, and in fact a considerable fraction of isolated CTCs did not express epithelial markers. The RUBYchip™ can overcome the limitations of label-dependent technologies and improve the identification of CTC subpopulations that may be related to different clinical outcomes.
Highlights
Gastrointestinal (GI) cancers can develop from any anatomic sites of the digestive system, ranking as some of the most frequently diagnosed cancer types worldwide and constituting a group of highest morbidity [1]
We have shown that circulating tumor cells (CTCs) can be efficiently isolated in less than 1 h and in a label-free manner from patients with metastatic GI using this technology
That in clinical samples, a considerable fraction of the isolated CTCs was negative for classical epithelial biomarkers and positive for epithelial-tomesenchymal transition (EMT) biomarkers
Summary
Gastrointestinal (GI) cancers can develop from any anatomic sites of the digestive system, ranking as some of the most frequently diagnosed cancer types worldwide and constituting a group of highest morbidity [1]. A considerable portion of early-stage GI cancer patients who undergo curative resection suffer metastatic disease within 5 years of surgery [4]. In gastric cancer in particular, approximately half of the patients develop metastasis within the first 5 years after surgery or suffer from severe treatment side-effects [5]. This might indicate that either an occult metastatic process is occurring in parallel with primary tumor development (that went undetected through conventional diagnostic methodologies), or that tumor cells with metastatic potential have entered the bloodstream, causing subsequent local and/or distant metastasis [6,7]
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