National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions

Kagan, J., Moritz, R. L., Mazurchuk, R., Lee, J. H., Kharchenko, P. V., Rozenblatt-Rosen, O., Ruppin, E., Edfors, F., Ginty, F., Goltsev, Y., Wells, J. A., LaCava, J., Riesterer, J. L., Germain, R. N., Shi, T., Chee, M. S., Budnik, B. A., Yates, J. R., Chait, B. T., Moffitt, J. R., Smith, R. D., Srivastava, S. (May 2020) National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions. J Proteome Res, 19 (5). pp. 1900-1912. ISSN 1535-3893

Abstract

A Think-Tank Meeting was convened by the National Cancer Institute (NCI) to solicit experts' opinion on the development and application of multiomic single-cell analyses, and especially single-cell proteomics, to improve the development of a new generation of biomarkers for cancer risk, early detection, diagnosis, and prognosis as well as to discuss the discovery of new targets for prevention and therapy. It is anticipated that such markers and targets will be based on cellular, subcellular, molecular, and functional aberrations within the lesion and within individual cells. Single-cell proteomic data will be essential for the establishment of new tools with searchable and scalable features that include spatial and temporal cartographies of premalignant and malignant lesions. Challenges and potential solutions that were discussed included (i) The best way/s to analyze single-cells from fresh and preserved tissue; (ii) Detection and analysis of secreted molecules and from single cells, especially from a tissue slice; (iii) Detection of new, previously undocumented cell type/s in the premalignant and early stage cancer tissue microenvironment; (iv) Multiomic integration of data to support and inform proteomic measurements; (v) Subcellular organelles-identifying abnormal structure, function, distribution, and location within individual premalignant and malignant cells; (vi) How to improve the dynamic range of single-cell proteomic measurements for discovery of differentially expressed proteins and their post-translational modifications (PTM); (vii) The depth of coverage measured concurrently using single-cell techniques; (viii) Quantitation - absolute or semiquantitative? (ix) Single methodology or multiplexed combinations? (x) Application of analytical methods for identification of biologically significant subsets; (xi) Data visualization of N-dimensional data sets; (xii) How to construct intercellular signaling networks in individual cells within premalignant tumor microenvironments (TME); (xiii) Associations between intrinsic cellular processes and extrinsic stimuli; (xiv) How to predict cellular responses to stress-inducing stimuli; (xv) Identification of new markers for prediction of progression from precursor, benign, and localized lesions to invasive cancer, based on spatial and temporal changes within individual cells; (xvi) Identification of new targets for immunoprevention or immunotherapy-identification of neoantigens and surfactome of individual cells within a lesion.

Item Type: Paper
Additional Information: 1535-3907 Kagan, Jacob Orcid: 0000-0002-1294-9606 Moritz, Robert L Mazurchuk, Richard Lee, Je Hyuk Kharchenko, Peter Vasili Rozenblatt-Rosen, Orit Ruppin, Eytan Edfors, Fredrik Orcid: 0000-0002-0017-7987 Ginty, Fiona Goltsev, Yury Wells, James A Orcid: 0000-0001-8267-5519 LaCava, John Riesterer, Jessica L Germain, Ronald N Shi, Tujin Orcid: 0000-0002-5592-3588 Chee, Mark S Budnik, Bogdan A Yates, John R 3rd Orcid: 0000-0001-5267-1672 Chait, Brian T Moffitt, Jeffery R Smith, Richard D Srivastava, Sudhir R01 CA194600/CA/NCI NIH HHS/United States R01 CA208179/CA/NCI NIH HHS/United States Journal Article United States J Proteome Res. 2020 May 1;19(5):1900-1912. doi: 10.1021/acs.jproteome.0c00021. Epub 2020 Apr 2.
Uncontrolled Keywords: *biomarkers *clonal evolution *early detection *lesion’s heterogeneity *precancer *precursor lesion *single-cell mass spectrometry *single-cell proteomics *spatial and temporal cartography *targeted proteomics *targets for prevention and therapy *tumorigenic lesion
Subjects: bioinformatics
diseases & disorders
bioinformatics > genomics and proteomics
Investigative techniques and equipment
diseases & disorders > neoplasms
Investigative techniques and equipment > biomarker
diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > drugs and therapies > Immunotherapy
CSHL Authors:
Communities: CSHL labs > Lee lab
Depositing User: Matthew Dunn
Date: 1 May 2020
Date Deposited: 14 Dec 2020 16:13
Last Modified: 30 Jan 2024 21:10
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39693

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