Research Papers:

Single cell correlation analysis of liquid and solid biopsies in metastatic colorectal cancer

Anna S. Gerdtsson, Jana-Aletta Thiele, Stephanie N. Shishido, Serena Zheng, Randolph Schaffer, Kelly Bethel, Steven Curley, Heinz-Josef Lenz, Diana L. Hanna, Jorge Nieva, Anand Kolatkar, Carmen Ruiz, Mariam Rodriguez-Lee, Gerard J. Oakley III, Jerry S.H. Lee, James Hicks and Peter Kuhn

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Oncotarget. 2019; 10:7016-7030. https://doi.org/10.18632/oncotarget.27271

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Anna S. Gerdtsson1, Jana-Aletta Thiele2, Stephanie N. Shishido1, Serena Zheng1, Randolph Schaffer3, Kelly Bethel3, Steven Curley4, Heinz-Josef Lenz5, Diana L. Hanna5, Jorge Nieva5, Anand Kolatkar1, Carmen Ruiz1, Mariam Rodriguez-Lee1, Gerard J. Oakley III6, Jerry S.H. Lee5, James Hicks1 and Peter Kuhn1

1 USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA

2 Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic

3 Scripps MDAnderson Cancer Center, La Jolla, CA, USA

4 Division of Surgical Oncology, Baylor College of Medicine, Houston, TX, USA

5 Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

6 Diagnostic and Experimental Pathology, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA

Correspondence to:

Peter Kuhn,email: [email protected]

Keywords: single cell analysis; liquid biopsy; metastatic colorectal cancer; circulating tumor cells; cytomorphology

Received: July 10, 2019     Accepted: September 24, 2019     Published: December 17, 2019


As cancer care is transitioning to personalized therapies with necessary complementary or companion biomarkers there is significant interest in determining to what extent non-invasive liquid biopsies reflect the gold standard solid biopsy. We have established an approach for measuring patient-specific circulating and solid cell concordance by introducing tumor touch preparations to the High-Definition Single Cell Analysis workflow for high-resolution cytomorphometric characterization of metastatic colorectal cancer (mCRC). Subgroups of cells based on size, shape and protein expression were identified in both liquid and solid biopsies, which overall displayed high inter- and intra- patient pleomorphism at the single-cell level of analysis. Concordance of liquid and solid biopsies was patient-dependent and between 0.1-0.9. Morphometric variables displayed particularly high correlation, suggesting that circulating cells do not represent distinct subpopulations from the solid tumor. This was further substantiated by significant decrease in concentration of circulating cells after mCRC resection. Combined with the association of circulating cells with tumor burden and necrosis of hepatic lesions, our overall findings demonstrate that liquid biopsy cells can be informative biomarkers in the mCRC setting. Patient-specific level of concordance can readily be measured to establish the utility of circulating cells as biomarkers and define biosignatures for liquid biopsy assays.

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