Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology
<p>Components of an exosome. Exosomes contain a wide variety of molecules of different natures, such as nucleic acids, proteins, or lipids. All the content at both the membrane and soluble levels represents the cell of origin the exosome is release from.</p> "> Figure 2
<p>Liquid biopsy analytes. In the bloodstream, many components can be found, cellular or non-cellular in nature. Some of them constitute liquid biopsy analytes (marked with an asterisk). Higher concentrations of analytes (in parentheses) will facilitate isolation techniques and subsequent analysis. Data taken from [<a href="#B12-cancers-13-02147" class="html-bibr">12</a>].</p> "> Figure 3
<p>Five sources of exosomal heterogeneity. The heterogeneity of the exosomes results from the combination of five factors: the cell of origin from which they are released (organ and cell type of origin); their molecular composition; their size; their number; and the functionality triggered in recipient cells. Different combinations of these five factors make exosome heterogeneity highly complex.</p> "> Figure 4
<p>Hallmarks of exosomes in cancer. Tumor-derived exosomes have important functional roles in intercellular crosstalk, affecting the biology of their target cells in different manners. Through this crosstalk, exosomes drive the tumoral process and other pathological conditions. The picture summarizes responses that exosome uptake can trigger in the recipient cells (functional hallmarks).</p> "> Figure 5
<p>The role of exosomes in the tumor microenvironment. TEX communicate with their microenvironment. At a local level, exosomes can be uptaken by other adjoining tumor cells, favoring an EMT process (<b>a</b>). They may also modify the biology of stromal (<b>b</b>) and endothelial (<b>c</b>) cells by activating them to support the tumor. Exosomes received by immune cells favor an immunosuppressive microenvironment that helps tumor growth (<b>d</b>). Furthermore, exosomes can reach blood or lymphatic vessels and travel to distal organs, where they will educate native cells, preparing a premetastatic niche where subsequent circulating tumor cells (CTCs) will nest and grow (<b>e</b>).</p> ">
Abstract
:Simple Summary
Abstract
1. Exosome Biogenesis and Composition—Reflecting Their Origin
2. Exosomes: A Source of Biomarkers
3. Exosome Heterogeneity: An Unknown Wealth?
4. Sending a Message: The Role of Exosomes in Intercellular Communication
4.1. A Short-Range Shipment: The Role of Exosomes in the Tumor Microenvironment
4.2. A Long-Range Shipment: The Role of Exosomes in Metastatic Organs
5. TEX Biomarkers in Clinics: A List of Possibilities
6. Future Perspectives and Challenges: The Dawn of a New Era
Funding
Conflicts of Interest
References
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Traits | Liquid Biopsy Analyte | ||||
---|---|---|---|---|---|
CTCs 1 | ctDNA 2 | Exosomes | ctRNA 3 | miRNA | |
Origin | |||||
Viable cells | ✔ 4 | ✖ 5 | ✔ | ? 6 | ? |
Apoptotic cells | ✔ | ✔ | ? | ? | ? |
Components | |||||
DNA | ✔ | ✔ | ✔ | N.A. 7 | N.A. |
RNA | ✔ | N.A. | ✔ | ✔ | ✔ |
Proteins | ✔ | N.A. | ✔ | N.A. | N.A. |
Metabolites | ✔ | N.A. | ? | N.A. | N.A. |
Extractable information | |||||
Copy number variation | ✔ | ✔ | ✔ | ✖ | ✖ |
Mutations | ✔ | ✔ | ✔ | ✔ | ✖ |
Epigenetic information | ✔ | ✔ | ✔ | ✖ | ✖ |
Fusion genes | ✔ | ✔ | ✔ | ✔ | ✖ |
Splice variants | ✔ | ✖ | ✔ | ✔ | ✖ |
Single-cell information | ✔ | ✖ | ✖ | ✖ | ✖ |
Application in personalized medicine | |||||
Diagnosis | ✔ | ✔ 8 | ✔ | ? | ✔ |
Classification of molecular subtypes | ✔ | ✔ | ? | ? | ✖ |
Clonal evolution tracking | ✔ | ✔ | ? | ✖ | ✖ |
Prognosis | ✔ | ✔ | ✔ | ? | ✔ |
Recurrence | ✔ | ✔ | ✔ | ✔ | ✖ |
Predictive | ✔ | ✔ | ✔ | ? | ✖ |
Resistance prediction | ✔ | ✔ | ✔ | ? | ✖ |
Monitoring treatment | ✔ | ✔ | ✔ | ? | ? |
Exosomal miRNAs as Cancer Biomarkers | ||||
miRNA | Cancer type | Clinical value | Biofluid | Reference |
Let-7b-5p, -122-5p, -146b-5p, -210-3p, -215-5p | Breast cancer | Diagnosis | Plasma | [84] |
miR-224 | Hepatocellular carcinoma | Diagnosis/Prognosis | Serum | [85] |
miR-106b, miR-1269a | Lung cancer | Diagnosis/Prognosis | Serum | [86,87] |
miR-375, -1307 | Ovarian cancer | Diagnosis | Serum | [88] |
Exosomal lncRNAs as Cancer Biomarkers | ||||
lncRNA | Cancer type | Clinical value | Biofluid | Reference |
PCAT-1, UBC1 and SNHG16 | Bladder cancer | Diagnosis/Prognosis | Urine | [89] |
MALAT-1 | Lung cancer | Diagnosis | Serum | [90] |
Exosomal mRNA as Cancer Biomarkers | ||||
mRNA | Cancer type | Clinical value | Biofluid | Reference |
BRAF, KRAS (mutant) | Colorectal cancer | Diagnosis | Serum | [91] |
Exosomal mutated DNA as Cancer Biomarkers | ||||
DNA | Cancer type | Clinical value | Biofluid | Reference |
IDH1 | Glioblastoma | Diagnosis/Prognosis | Plasma | [92] |
EGFR | Lung cancer | Diagnosis/Prognosis | Plasma/Bronchioalveolar lavage | [93,94,95,96] |
BRAF | Melanoma | Therapeutic monitoring | Plasma | [97] |
KRAS, P53 | Pancreatic cancer | Diagnosis/Prognosis | Serum/Plasma | [98,99] |
MYC, P53, MLH1, PTEN, AR | Prostate cancer | Diagnosis/Prognosis | Plasma | [100,101] |
Exosomal proteins as Cancer Biomarkers | ||||
Protein | Cancer type | Clinical value | Biofluid | Reference |
PDL-1 | Melanoma | Prognosis | Plasma | [102] |
Factors | Ultracentrifugation | Precipitation | Affinity | Microfluidic | Filtration | |||
---|---|---|---|---|---|---|---|---|
Differential | Gradient | Immune | Flow Cytometry | Ultrafiltration | Molecular Exclusion | |||
Purity | low | high | low | high | high | high | low | high |
Yield | medium | low | medium | medium | medium | low | medium | high |
Specialized equipment | medium | medium | high | medium | low | low | high | high |
Specialized user | medium | low | high | medium | medium | medium | high | high |
RNA characterization | high | high | high | high | high | high | high | high |
Protein characterization | medium | high | low | high | high | high | medium | high |
Functional studies | medium | medium | low | medium | medium | medium | medium | high |
Scalability | medium | low | high | medium | high | low | medium | medium |
Time | medium | low | high | medium | low | medium | high | medium |
Cost | high | medium | high | low | low | low | medium | medium |
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Valencia, K.; Montuenga, L.M. Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology. Cancers 2021, 13, 2147. https://doi.org/10.3390/cancers13092147
Valencia K, Montuenga LM. Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology. Cancers. 2021; 13(9):2147. https://doi.org/10.3390/cancers13092147
Chicago/Turabian StyleValencia, Karmele, and Luis M. Montuenga. 2021. "Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology" Cancers 13, no. 9: 2147. https://doi.org/10.3390/cancers13092147
APA StyleValencia, K., & Montuenga, L. M. (2021). Exosomes in Liquid Biopsy: The Nanometric World in the Pursuit of Precision Oncology. Cancers, 13(9), 2147. https://doi.org/10.3390/cancers13092147