Open Access

Laura De Vargas Roditi, Andrea Jacobs, Jan Hendrik Rueschoff, Pete Bankhead, Stéphane Chevrier, Hartland W. Jackson, Thomas Hermanns, Christian D. Fankhauser, Cedric Poyet, Felix Chun, Niels Jan Felix Rupp, Alexandra Tschäbunin, Bernd Bodenmiller, Peter Johannes Wild

• Localized prostate cancer exhibits multiple genomic alterations and heterogeneity at the proteomic level. Single-cell technologies capture important cell-to-cell variability responsible for heterogeneity in biomarker expression that may be overlooked when molecular alterations are based on bulk tissue samples. This study aims to identify prognostic biomarkers and describe the heterogeneity of prostate cancer and the associated microenvironment by simultaneously quantifying 36 proteins using single-cell mass cytometry analysis of over 1.6 million cells from 58 men with localized prostate cancer. We perform this task, using a high-dimensional clustering pipeline named Franken to describe subpopulations of immune, stromal, and prostate cells, including changes occurring in tumor tissues and high-grade disease that provide insights into the coordinated progression of prostate cancer. Our results further indicate that men with localized disease already harbor rare subpopulations that typically occur in castration-resistant and metastatic disease.