Abstract
We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs.
Highlights
A staggering 90% of cancer deaths are attributable to metastases [1]
We reported additional model evaluation metrics such as F1 score, Mathews correlation coefficient (MCC) and Cohen’s kappa as applicable (Supplementary Table S4)
As control, expression profiles of human peripheral blood mononuclear cell (PBMC) were collected from six different studies (Supplementary Table S1)
Summary
After detaching from solid tumors, cancer cells travel through the bloodstream to reach distant organs and seed the development of metastatic tumors [2]. Cancer cells under circulation are called circulating tumor cells (CTCs) [3]. As a blood-based bio marker, CTCs offer unabated, real-time insights into tumor evolution and therapeutic responses. Despite these promises, the rareness of CTCs in the peripheral blood hinders their isolation and characterization [3]. Cancers in solid tissues develop from epithelial cells, which are typically densely packed in layers. Dissemination and migration of cancer cells during metastasis require the acquisition of mesenchymal-like features. Transcendence of epithelial cancer cells into mesenchymal-like ones is popularly known as Epithelial to Mesenchymal Transition (EMT)
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