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Cancer cell profiling by barcoding allows multiplexed protein analysis in fine-needle aspirates.


ABSTRACT: Immunohistochemistry-based clinical diagnoses require invasive core biopsies and use a limited number of protein stains to identify and classify cancers. We introduce a technology that allows analysis of hundreds of proteins from minimally invasive fine-needle aspirates (FNAs), which contain much smaller numbers of cells than core biopsies. The method capitalizes on DNA-barcoded antibody sensing, where barcodes can be photocleaved and digitally detected without any amplification steps. After extensive benchmarking in cell lines, this method showed high reproducibility and achieved single-cell sensitivity. We used this approach to profile ~90 proteins in cells from FNAs and subsequently map patient heterogeneity at the protein level. Additionally, we demonstrate how the method could be used as a clinical tool to identify pathway responses to molecularly targeted drugs and to predict drug response in patient samples. This technique combines specificity with ease of use to offer a new tool for understanding human cancers and designing future clinical trials.

SUBMITTER: Ullal AV 

PROVIDER: S-EPMC4063286 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Cancer cell profiling by barcoding allows multiplexed protein analysis in fine-needle aspirates.

Ullal Adeeti V AV   Peterson Vanessa V   Agasti Sarit S SS   Tuang Suan S   Juric Dejan D   Castro Cesar M CM   Weissleder Ralph R  

Science translational medicine 20140101 219


Immunohistochemistry-based clinical diagnoses require invasive core biopsies and use a limited number of protein stains to identify and classify cancers. We introduce a technology that allows analysis of hundreds of proteins from minimally invasive fine-needle aspirates (FNAs), which contain much smaller numbers of cells than core biopsies. The method capitalizes on DNA-barcoded antibody sensing, where barcodes can be photocleaved and digitally detected without any amplification steps. After ext  ...[more]

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