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Multiplex protein detection on circulating tumor cells from liquid biopsies using imaging mass cytometry. 2018
Erik Gerdtsson, and
Milind Pore, and
Jana-Aletta Thiele, and
Anna Sandström Gerdtsson, and
Paymaneh D Malihi, and
Rafael Nevarez, and
Anand Kolatkar, and
Carmen Ruiz Velasco, and
Sophia Wix, and
Mohan Singh, and
Anders Carlsson, and
Amado J Zurita, and
Christopher Logothetis, and
Akil A Merchant, and
James Hicks, and
Peter Kuhn
Bridge@USC, USC David and Dana Dornsife College of Letters, Arts, and Sciences, 3430 S Vermont Ave, TRF 114, MC3303, Los Angeles, CA, 90089-3303; gerdtsso@usc.edu; pore@usc.edu; agerdtss@usc.edu; pmalihi@usc.edu; rnevarez@usc.edu; kolatkar@usc.edu; ruizvela@usc.edu; swix@usc.edu; ncarlsso@usc.edu; jameshic@usc.edu; pkuhn@usc.edu.
Molecular analysis of circulating and disseminated tumor cells (CTCs/DTCs) has great potential as a means for continuous evaluation of prognosis and treatment efficacy in near-real time through minimally invasive liquid biopsies. To realize this potential, however, methods for molecular analysis of these rare cells must be developed and validated. Here, we describe the integration of imaging mass cytometry (IMC) using metal-labeled antibodies as implemented on the Fluidigm Hyperion Imaging System into the workflow of the previously established High Definition Single Cell Analysis (HD-SCA) assay for liquid biopsies, along with methods for image analysis and signal normalization. Using liquid biopsies from a metastatic prostate cancer case, we demonstrate that IMC can extend the reach of CTC characterization to include dozens of protein biomarkers, with the potential to understand a range of biological properties that could affect therapeutic response, metastasis and immune surveillance when coupled with simultaneous phenotyping of thousands of leukocytes.
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