Single-Cell Identification of Melanoma Biomarkers in Circulating Tumor Cells

Cancers (Basel). 2022 Oct 8;14(19):4921. doi: 10.3390/cancers14194921.

Abstract

The current standard for investigating tumors is surgical biopsy, which is costly, invasive, and difficult to perform serially. As an adjunct, circulating tumor cells (CTCs)-cells that have broken away from the primary tumor or metastatic sites-can be obtained from a blood draw and offer the potential for obtaining serial genetic information and serving as biomarkers. Here, we detail the potential for melanoma CTCs to serve as biomarkers and discuss a clinically viable methodology for single-cell CTC isolation and analysis that overcomes previous limitations. We explore the use of melanoma CTC biomarkers by isolating and performing single-cell RNA sequencing on CTCs from melanoma patients. We then compared transcriptional profiles of single melanoma CTCs against A375 cells and peripheral blood mononuclear cells to identify unique genes differentially regulated in circulating melanoma tumor cells. The information that can be obtained via analysis of these CTCs has significant potential in disease tracking.

Keywords: circulating tumor cells (CTCs); immune checkpoint blockade; liquid biopsy; melanoma; microarray; negative enrichment; single-cell RNA-seq.

Grants and funding

This research was funded by the following sources: The Cancer Research Institute, Clinic & Laboratory Integration Program (CLIP), The American Cancer Society, grant numbers. 129523-MRSG-16-029-01-DDC and TLC-21-003-01-TLC, The Department of Defense (DOD) Congressionally Directed Medical Research Program (CDMRP) grant numbers W81XWH-17-1-0514 and W81XWH-17-1-0098, The Melanoma Research Alliance, grant number 344442, The OHSU Physician-Scientist Program, and the Cancer Advanced Research Early Detection Center (CEDAR) at OHSU.