Abstract LB-023: Describing prostate cancer heterogeneity through single cell analysis with mass cytometry

Background Single-cell analysis has emerged as a crucial approach to detect variations in genetic and proteomic expression. Prostate cancer is characterized by multiple genomic alterations leading to the complex nature of the disease. The heterogeneity at the proteomic level is not yet well characterized, yet intra-tumor heterogeneity can impair correct diagnosis and treatment, by driving therapy resistance. Meanwhile inter-tumor heterogeneity can strongly impact personalization of treatments highlighting the importance of characterizing both intra- and inter-tumor heterogeneity. Using single-cell mass cytometry data, we identify the proteomic profiles of the different cellular subpopulations found in prostate cancer that are common across a cohort of 50 patients while also describing the variations across patients, thus thoroughly characterizing prostate tumor heterogeneity. Methods & Results Mass cytometry experiments allow quantification of dozens of proteins simultaneously at the single-cell level, for thousands of cells. The high dimensionality of this data represents a challenge for data visualization and clustering, which require computational approaches for interpretation of the results. We developed a new computational method to address this task and analyzed tissue sections from surgically removed prostates from 50 patients using mass cytometry with a comprehensive set of 40 antibodies to jointly identify surface markers, enzymes, transcription factors and functional readouts. Conclusions Here, we present for the first time an analysis of prostate tumor cell heterogeneity by mass cytometry coupled to a newly developed computational method that improves visualization and clustering of such high-dimensional data. This study was conducted by analyzing prostate cancer samples from fifty patients at the single-cell level using mass cytometry to estimate the abundance of forty different proteins simultaneously for each cell. Our results show that immune, stromal and epithelial cells can be comprehensively distinguished across all patients. A closer look at the epithelial compartment reveals multiple subpopulations which we describe in terms of their protein expression patterns to characterize the intra- and inter-tumor heterogeneity in prostate cancer. This work demonstrates how single cell phenotypic profiles of prostate tumor cells, taken from surgically removed prostates, can be used to quantify the varying heterogeneity during tumor progression. Citation Format: Laura De Vargas Roditi, Andrea Jacobs, Christian Fankhauser, Cedric Poyet, Peter Wild, Bernd Bodenmiller. Describing prostate cancer heterogeneity through single cell analysis with mass cytometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-023.