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    Nanonets for multiomics blood analysis and cancer biomarker discovery

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    Authors
    Gardner, L.
    Rothwell, Dominic G
    Dive, Caroline
    Kostarelos, K.
    Hadjidemetriou, M.
    Affiliation
    University of Manchester, Manchester
    Issue Date
    2021
    
    Metadata
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    Abstract
    Despite the tremendous potential of liquid biopsies to revolutionise cancer care, there has been limited success translating blood-circulating proteomic and genomic biomarkers into the clinic. This is fundamentally due to the extremely low concentration of tumour-derived biomolecules in blood circulation, particularly at an early disease stage, which makes the discovery phase of the biomarker pipeline extremely challenging. Nanotechnology offers a promising solution, with a nanoparticle-biomolecule enrichment tool recently developed to enrich low-abundant, low molecular weight proteins in the blood of ovarian cancer patients.[1] Proteomic analysis followed by immunoassay-based validation of selected proteins demonstrated the potential of the nanoparticle-platform proposed to discover novel biomarkers with greater specificity and sensitivity than the clinically used biomarkers. In addition, we recently confirmed the presence of cell-free DNA (cfDNA) captured onto the surface lipid nanoparticles incubated ex vivo with human plasma.[2] A significantly higher abundance of cfDNA was detected in the nanoparticle-enriched plasma samples of late-stage ovarian cancer patients compared to age-matched female controls. Proteomic analysis of the same samples also revealed tumour-specific elevations in histone proteins, which are commonly found in circulation complexed with cfDNA. These findings have highlighted the opportunity for the development of a nano-proteogenomics platform able to simultaneously purify both proteins and cell-free nucleic acids from human plasma, an important step in the discovery of novel multi-omic biomarker panels. Utilising the above patented nanotechnology, we have compared proteomic and genomic profiles derived from nanoparticle-biomolecule samples of cancer patients with age- and sex-matched controls to uncover new potential blood-based biomarkers in a proof-of-principle study. In brief, ex-vivo plasma samples were incubated with lipid-based nanoparticles and purified using a two-step size-based purification protocol. The purified samples were then analysed by label-free proteomics (LC-MS/MS) and next-generation sequencing to uncover both proteomic and genomic tumour-specific signatures, including differentially abundant proteins, genomic copy number alterations and tumour-specific mutations. This work highlights the potential of our nanotechnology-based enrichment platform to enhance the discovery of cancer-specific proteogenomic biomarker panels, a vital step in developing sensitive and specific liquid biopsies for the early detection of cancer.
    Citation
    Gardner L, Rothwell DG, Dive C, Kostarelos K, Hadjidemetriou M. Abstract 568: Nanonets for multiomics blood analysis and cancer biomarker discovery. In: Clinical Research (Excluding Clinical Trials). American Association for Cancer Research; 2021.
    Journal
    Cancer Research
    URI
    http://hdl.handle.net/10541/624643
    DOI
    10.1158/1538-7445.AM2021-568
    Additional Links
    https://dx.doi.org/10.1158/1538-7445.AM2021-568
    Type
    Other
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1538-7445.AM2021-568
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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