Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach.
| Title: | Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach. |
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| Authors: | Domenyuk V; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Zhong Z; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Stark A; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Xiao N; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; O'Neill HA; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Wei X; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Wang J; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Tinder TT; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Tonapi S; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Duncan J; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Hornung T; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Hunter A; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Miglarese MR; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Schorr J; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Halbert DD; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; Quackenbush J; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Smith 822A, Boston, MA 02215, USA.; Department of Biostatistics, Harvard School of Public Health, 655 Huntington Ave, Boston, MA 0211, USA.; Poste G; Complex Adaptive Systems Initiative, Arizona State University, 1475 N. Scottsdale Rd., Suite 361, Scottsdale, AZ 85257, USA.; Berry DA; Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.; Mayer G; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; LIMES Program Unit Chemical Biology &Medicinal Chemistry, c/o Kekulé Institut für Organische Chemie und Biochemie, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.; Famulok M; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA.; LIMES Program Unit Chemical Biology &Medicinal Chemistry, c/o Kekulé Institut für Organische Chemie und Biochemie, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.; Chemical Biology Max-Planck-Fellowship Group, Center of Advanced European Studies and Research (CAESAR), Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.; Spetzler D; Caris Life Sciences, 4610 South 44th Place, Phoenix, AZ 85040, USA. |
| Source: | Scientific reports [Sci Rep] 2017 Feb 20; Vol. 7, pp. 42741. Date of Electronic Publication: 2017 Feb 20. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Nature Publishing Group, copyright 2011- |
| MeSH Terms: | Breast Neoplasms/*blood ; Exosomes/*genetics ; Oligodeoxyribonucleotides/*metabolism ; Systems Biology/*methods; Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics ; Area Under Curve ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; SELEX Aptamer Technique ; Sequence Analysis, DNA |
| Abstract: | Technologies capable of characterizing the full breadth of cellular systems need to be able to measure millions of proteins, isoforms, and complexes simultaneously. We describe an approach that fulfils this criterion: Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT). ADAPT employs an enriched library of single-stranded oligodeoxynucleotides (ssODNs) to profile complex biological samples, thus achieving an unprecedented coverage of system-wide, native biomolecules. We used ADAPT as a highly specific profiling tool that distinguishes women with or without breast cancer based on circulating exosomes in their blood. To develop ADAPT, we enriched a library of ~1011 ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 106 enriched ssODNs were then profiled against plasma from independent groups of healthy and breast cancer-positive women. ssODN-mediated affinity purification and mass spectrometry identified low-abundance exosome-associated proteins and protein complexes, some with known significance in both normal homeostasis and disease. Sequencing of the recovered ssODNs provided quantitative measures that were used to build highly accurate multi-analyte signatures for patient classification. Probing plasma from 500 subjects with a smaller subset of 2000 resynthesized ssODNs stratified healthy, breast biopsy-negative, and -positive women. An AUC of 0.73 was obtained when comparing healthy donors with biopsy-positive patients. |
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| Grant Information: | U01 CA190234 United States CA NCI NIH HHS; U01 CA151118 United States CA NCI NIH HHS; U24 CA194354 United States CA NCI NIH HHS; P30 CA016672 United States CA NCI NIH HHS; R35 CA197449 United States CA NCI NIH HHS; UL1 TR000371 United States TR NCATS NIH HHS |
| Substance Nomenclature: | 0 (Biomarkers, Tumor); 0 (Oligodeoxyribonucleotides) |
| Entry Date(s): | Date Created: 20170221 Date Completed: 20181029 Latest Revision: 20190827 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5316983 |
| DOI: | 10.1038/srep42741 |
| PMID: | 28218293 |
| Database: | MEDLINE |
Journal Article