Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach

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.

Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma

“…It has been difficult to assess the longitudinal impact of biobehavioral factors such as social support on tumor dynamics because of the lack of reliable circulating blood biomarkers of tumor biology. The use of exosomal profiling represents a novel strategy for in vivo monitoring of tumor biology and for the assessment of dynamic changes occurring in tumor cells in the context of biobehavioral factors . Exosomes are intact cell‐derived vesicles shed from both normal and tumor cells that are involved in intercellular signaling .…”

The current state of molecular testing in the treatment of patients with solid tumors, 2019

“…Regarding extracellular vesicles or exosomes, a newly developed, minimally invasive ADAPT Biotargeting System characterizes complex biological systems in their inherent state(s) and relies on the fact that a large number of cells in the body secrete extracellular vesicles into the circulation, and the molecular composition of these “exosomes” correlates with the cell of origin. Through intercellular communication, exosomes play a part in controlling many tumor progressive processes, including immune evasion, angiogenesis, and metastasis . The ADAPT assay has been shown to have potential for biomarker identification and therapeutic use across most cancer types …”

“…Through intercellular communication, exosomes play a part in controlling many tumor progressive processes, including immune evasion, angiogenesis, and metastasis . The ADAPT assay has been shown to have potential for biomarker identification and therapeutic use across most cancer types …”

“…The Liquid Biopsy: Circulating Tumor Cells and Exosomes Peripheral blood samples are a biomarker source by way of circulating tumor cells (DNA) and circulating nucleic acids or associated extracellular vesicles or exosomes. [169][170][171] The use of liquid biopsy profiling has proven useful in selected clinical scenarios but, to date, despite its potential in the management of patients with most metastatic solid tumors, this technique has not established a firm role in standard practice. Obvious advantages include ease of access to the tissue through a simple blood draw.…”

“…Through intercellular communication, exosomes play a part in controlling many tumor progressive processes, including immune evasion, angiogenesis, and metastasis. 171 The ADAPT assay has been shown to have potential for biomarker identification and therapeutic use across most cancer types. 171,172 Community Hospital Molecular Testing and Assessment Program Because 85% of cancer care is delivered in a community setting, it is imperative that the programmatic decisions concerning molecular testing for cancer include standardization, physician engagement, and application to point of care.…”