Extracellular Vesicles’ Genetic Cargo as Noninvasive Biomarkers in Cancer: A Pilot Study Using ExoGAG Technology
Abstract
:1. Introduction
2. Materials and Methods
2.1. Isolation of EVs from Plasma and Urine Samples Using ExoGAG
2.2. EVs’ Production and Isolation from HCT116 Human Colorectal Cancer Cell Line by Ultracentrifugation
2.3. Characterization of EVs Isolated from Plasma and Urine Samples Using ExoGAG Technology
2.3.1. NTA Nanosight NS300 (NTA)
2.3.2. Flow Cytometry Analysis
2.4. EV-DNA Purification and Droplet Digital PCR (ddPCR) Analysis
2.5. EV-RNA Purification and Quantitative Real-Time PCR (RT-q-PCR)
2.6. Gene Expression Analysis Using nCounter NanoString
3. Results
3.1. Isolation and Characterization of EVs from Plasma and Urine Samples Using ExoGAG
3.1.1. Characterization of EVs from Plasma Samples
3.1.2. Characterization of EVs from Urine Samples
3.2. Point Mutation Detection by Droplet Digital PCR (ddPCR) in DNA from Plasma EVs Isolated by ExoGAG
3.3. Optimization of Plasma and Urine EV-RNA Purification Methodologies
3.4. EV-mRNA Analysis Using nCounter PanCancer Pathways Panel
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Honoré, N.; Rachel Galot, R.; van Marcke, C.; Limaye, N.; Machiels, J.P. Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact. Cancers 2021, 13, 5364. [Google Scholar] [CrossRef] [PubMed]
- Choucair, K.; Mattar, B.I.; Van Truong, Q.; Koeneke, T.; Van Truong, P.; Dakhil, C.; Cannon, M.W.; Joel Page, S.; Deutsch, J.M.; Carlson, E.; et al. Liquid Biopsy-based Precision Therapy in Patients with Advanced Solid Tumors: A Real-world Experience from a Community-based Oncology Practice. Oncologist 2022, 27, 183–190. [Google Scholar] [CrossRef]
- Lone, A.N.; Nisar, S.; Masoodi, T.; Singh, M.; Rizwan, A.; Hashem, S.; El-Rifai, W.; Bedognetti, D.; Batra, S.K.; Haris, M.; et al. Liquid biopsy: A step closer to transform diagnosis, prognosis and future of cancer treatments. Mol. Cancer 2022, 21, 79. [Google Scholar] [CrossRef] [PubMed]
- Ignatiadis, M.; Sledge, G.W.; Jeffrey, S.S. Liquid biopsy enters the clinic—Implementation issues and future challenges. Nat. Rev. Clin. Oncol. 2021, 18, 297–312. [Google Scholar] [CrossRef]
- Dianat-Moghadam, H.; Azizi, M.; Eslami-S, Z.; Cortés-Hernández, L.E.; Heidarifard, M.; Nouri, M.; Alix-Panabières, C. The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance. Cancers 2020, 12, 867. [Google Scholar] [CrossRef] [Green Version]
- Kalikaki, A.; Politaki, H.; Souglakos, J.; Apostolaki, S.; Papadimitraki, E.; Georgoulia, N.; Tzardi, M.; Mavroudis, D.; Georgoulias, V.; Voutsina, A. KRAS Genotypic Changes of Circulating Tumor Cells during Treatment of Patients with Metastatic Colorectal Cancer. PLoS ONE 2014, 9, e104902. [Google Scholar] [CrossRef]
- Kruijff, I.E.; Sieuwerts, A.M.; Onstenk, W.; Jager, A.; Hamberg, P.; Jongh, F.E.; Smid, M.; Kraan, J.; Timmermans, M.A.; Martens, J.W.M.; et al. Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer. Int. J. Cancer 2019, 145, 1083–1089. [Google Scholar] [CrossRef]
- Guibert, N.; Delaunay, M.; Lusque, A.; Boubekeur, N.; Rouquette, I.; Clermont, E.; Mourlanette, J.; Gouin, S.; Dormoy, I.; Favre, G.; et al. PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. Lung Cancer 2018, 120, 108–112. [Google Scholar] [CrossRef]
- Pereira-Veiga, T.; González-Conde, M.; León-Mateos, L.; Piñeiro-Cid, R.; Abuín, C.; Muinelo-Romay, L.; Martínez-Fernández, M.; Brea Iglesias, J.; García González, J.; Anido, U.; et al. Longitudinal CTCs gene expression analysis on metastatic castration-resistant prostate cancer patients treated with docetaxel reveals new potential prognosis markers. Clin. Exp. Metastasis 2021, 38, 239–251. [Google Scholar] [CrossRef]
- Kwan, T.T.; Bardia, A.; Spring, L.M.; Giobbie-Hurder, A.; Kalinich, M.; Dubash, T.; Sundaresan, T.; Hong, X.; LiCausi, J.A.; Ho, U.; et al. A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic Response in Localized and Metastatic Breast Cancer. Cancer Discov. 2018, 8, 1286–1299. [Google Scholar] [CrossRef]
- Menarini Silicon Biosystems, I. 2021. Available online: https://www.cellsearchctc.com/ (accessed on 10 October 2022).
- García-Olmo, D.; González-Masiá, J.A.; García-Olmo, D.C. Circulating nucleic acids in plasma and serum (CNAPS): Applications in oncology. OncoTargets Ther. 2013, 6, 819–832. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, X.; Li, C.; Zhang, Z.; Li, D.Y.; Du, J.; Ding, P.; Meng, H.; Xu, H.; Li, R.; Ho, E.; et al. Kinetics of plasma cfDNA predicts clinical response in non-small cell lung cancer patients. Sci. Rep. 2021, 11, 7633. [Google Scholar] [CrossRef] [PubMed]
- Flamini, E.; Mercatali, L.; Nanni, O.; Calistri, D.; Nunziatini, R.; Zoli, W.; Rosetti, P.; Gardini, N.; Lattuneddu, A.; Verdecchia, G.M.; et al. Free DNA and Carcinoembryonic Antigen Serum Levels: An Important Combination for Diagnosis of Colorectal Cancer. Clin. Cancer Res. 2006, 12, 6985–6988. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernandez-Garcia, D.; Hills, A.; Page, K.; Hastings, R.K.; Toghill, B.; Goddard, K.S.; Ion, C.; Ogle, O.; Boydell, A.R.; Gleason, K.; et al. Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer. Breast Cancer Res. 2019, 21, 149. [Google Scholar] [CrossRef]
- Schwarzenbach, H.; Hoon, D.S.B.; Pantel, K. Cell-free nucleic acids as biomarkers in cancer patients. Nat. Rev. Cancer 2011, 11, 426–437. [Google Scholar] [CrossRef] [PubMed]
- Tie, J.; Cohen, J.D.; Wang, Y.; Christie, M.; Simons, K.; Lee, M.; Wong, R.; Kosmider, S.; Ananda, S.; McKendrick, J.; et al. Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. JAMA Oncol. 2019, 5, 1710. [Google Scholar] [CrossRef]
- Garcia-Murillas, I.; Schiavon, G.; Weigelt, B.; Ng, C.; Hrebien, S.; Cutts, R.J.; Cheang, M.; Osin, P.; Nerurkar, A.; Kozarewa, I.; et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci. Transl. Med. 2015, 7, 302ra133. [Google Scholar] [CrossRef] [PubMed]
- Maas, S.L.N.; Breakefield, X.O.; Weaver, A.M. Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol. 2017, 27, 172–188. [Google Scholar] [CrossRef] [Green Version]
- Becker, A.; Thakur, B.K.; Weiss, J.M.; Kim, H.S.; Peinado, H.; Lyden, D. Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis. Cancer Cell 2016, 30, 836–848. [Google Scholar] [CrossRef] [Green Version]
- Nogués, L.; Benito-Martin, A.; Hergueta-Redondo, M.; Peinado, H. The influence of tumour-derived extracellular vesicles on local and distal metastatic dissemination. Mol. Aspects Med. 2018, 60, 15–26. [Google Scholar] [CrossRef]
- Boussadia, Z.; Lamberti, J.; Mattei, F.; Pizzi, E.; Puglisi, R.; Zanetti, C.; Pasquini, L.; Fratini, F.; Fantozzi, L.; Felicetti, F.; et al. Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules. J. Exp. Clin. Cancer Res. 2018, 37, 245. [Google Scholar] [CrossRef] [PubMed]
- Castellanos-Rizaldos, E.; Grimm, D.G.; Tadigotla, V.; Hurley, J.; Healy, J.; Neal, P.L.; Sher, M.; Venkatesan, R.; Karlovich, C.; Raponi, M.; et al. Exosome-Based Detection of EGFR T790M in Plasma from Non–Small Cell Lung Cancer Patients. Clin. Cancer Res. 2018, 24, 2944–2950. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wan, Y.; Liu, B.; Lei, H.; Zhang, B.; Wang, Y.; Huang, H.; Chen, S.; Feng, Y.; Zhu, L.; Gu, Y.; et al. Nanoscale extracellular vesicle-derived DNA is superior to circulating cell-free DNA for mutation detection in early-stage non-small-cell lung cancer. Ann. Oncol. 2018, 29, 2379–2383. [Google Scholar] [CrossRef] [PubMed]
- Yang, S.; Che, S.P.Y.; Kurywchak, P.; Tavormina, J.L.; Gansmo, L.B.; Correa de Sampaio, P.; Tachezy, M.; Bockhorn, M.; Gebauer, F.; Haltom, A.R.; et al. Detection of mutant KRAS and TP53 DNA in circulating exosomes from healthy individuals and patients with pancreatic cancer. Cancer Biol. Ther. 2017, 18, 158–165. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stephenson Clarke, J.R.; Douglas, L.R.; Duriez, P.J.; Balourdas, D.-I.; Joerger, A.C.; Khadiullina, R.; Bulatov, E.; Baud, M. Discovery of Nanomolar-Affinity Pharmacological Chaperones Stabilizing the Oncogenic p53 Mutant Y220C. ACS Pharmacol. Transl. Sci. 2022, 5, 1169–1180. [Google Scholar] [CrossRef] [PubMed]
- Arroyo, J.D.; Chevillet, J.R.; Kroh, E.M.; Ruf, I.K.; Pritchard, C.C.; Gibson, D.F.; Mitchell, P.S.; Bennett, C.F.; Pogosova-Agadjanyan, E.L.; Stirewalt, D.L.; et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. USA 2011, 108, 5003–5008. [Google Scholar] [CrossRef] [Green Version]
- Vickers, K.C.; Palmisano, B.T.; Shoucri, B.M.; Shamburek, R.D.; Remaley, A.T. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell Biol. 2011, 13, 423–433. [Google Scholar] [CrossRef] [Green Version]
- Kosaka, N.; Kogure, A.; Yamamoto, T.; Urabe, F.; Usuba, W.; Prieto-Vila, M.; Ochiya, T. Exploiting the message from cancer: The diagnostic value of extracellular vesicles for clinical applications. Exp. Mol. Med. 2019, 51, 1–9. [Google Scholar] [CrossRef] [Green Version]
- Del Re, M.; Marconcini, R.; Pasquini, G.; Rofi, E.; Vivaldi, C.; Bloise, F.; Restante, G.; Arrigoni, E.; Caparello, C.; Bianco, M.G.; et al. PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC. Br. J. Cancer 2018, 118, 820–824. [Google Scholar] [CrossRef] [Green Version]
- Woo, H.-K.; Park, J.; Ku, J.Y.; Lee, C.H.; Sunkara, V.; Ha, H.K.; Cho, Y.-K. Urine-based liquid biopsy: Non-invasive and sensitive AR-V7 detection in urinary EVs from patients with prostate cancer. Lab Chip 2019, 19, 87–97. [Google Scholar] [CrossRef]
- McKiernan, J.; Donovan, M.J.; O’Neill, V.; Bentink, S.; Noerholm, M.; Belzer, S.; Skog, J.; Kattan, M.W.; Partin, A.; Andriole, G.; et al. A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. JAMA Oncol. 2016, 2, 882. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Herrero, C.; de la Fuente, A.; Casas-Arozamena, C.; Sebastian, V.; Prieto, M.; Arruebo, M.; Abalo, A.; Colás, E.; Moreno-Bueno, G.; Gil-Moreno, A.; et al. Extracellular Vesicles-Based Biomarkers Represent a Promising Liquid Biopsy in Endometrial Cancer. Cancers 2019, 11, 2000. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mercadal, M.; Herrero, C.; López-Rodrigo, O.; Castells, M.; de la Fuente, A.; Vigués, F.; Bassas, L.; Larriba, S. Impact of Extracellular Vesicle Isolation Methods on Downstream miRNA Analysis in Semen: A Comparative Study. Int. J. Mol. Sci. 2020, 21, 5949. [Google Scholar] [CrossRef] [PubMed]
- Mariscal, J.; Fernandez-Puente, P.; Calamia, V.; Abalo, A.; Santacana, M.; Matias-Guiu, X.; Lopez-Lopez, R.; Gil-Moreno, A.; Alonso-Alconada, L.; Abal, M. Proteomic Characterization of Epithelial-Like Extracellular Vesicles in Advanced Endometrial Cancer. J. Proteome Res. 2019, 18, 1043–1053. [Google Scholar] [CrossRef] [PubMed]
- Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750. [Google Scholar] [CrossRef] [Green Version]
- Fernández-Llama, P.; Khositseth, S.; Gonzales, P.A.; Star, R.A.; Pisitkun, T.; Knepper, M.A. Tamm-Horsfall protein and urinary exosome isolation. Kidney Int. 2010, 77, 736–742. [Google Scholar] [CrossRef] [Green Version]
- Bracht, J.W.P.; Gimenez-Capitan, A.; Huang, C.-Y.; Potie, N.; Pedraz-Valdunciel, C.; Warren, S.; Rosell, R.; Molina-Vila, M.A. Analysis of extracellular vesicle mRNA derived from plasma using the nCounter platform. Sci. Rep. 2021, 11, 3712. [Google Scholar] [CrossRef]
- Wan, G.; Pehlke, C.; Pepermans, R.; Cannon, J.; Lidke, D.; Rajput, A. The H1047R point mutation in p110 alpha changes the morphology of human colon HCT116 cancer cells. Cell Death Discov. 2015, 1, 15044. [Google Scholar] [CrossRef] [Green Version]
- De Miguel Pérez, D.; Rodriguez Martínez, A.; Ortigosa Palomo, A.; Delgado Ureña, M.; Garcia Puche, J.L.; Robles Remacho, A.; Exposito Hernandez, J.; Lorente Acosta, J.A.; Ortega Sánchez, F.G.; Serrano, M.J. Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients. Sci. Rep. 2020, 10, 3974. [Google Scholar] [CrossRef] [Green Version]
- Thakur, B.K.; Zhang, H.; Becker, A.; Matei, I.; Huang, Y.; Costa-Silva, B.; Zheng, Y.; Hoshino, A.; Brazier, H.; Xiang, J.; et al. Double-stranded DNA in exosomes: A novel biomarker in cancer detection. Cell Res. 2014, 24, 766–769. [Google Scholar] [CrossRef]
- Yáñez-Mó, M.; Siljander, P.R.-M.; Andreu, Z.; Bedina Zavec, A.; Borràs, F.E.; Buzas, E.I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 2015, 4, 27066. [Google Scholar] [CrossRef] [Green Version]
- Todorova, D.; Simoncini, S.; Lacroix, R.; Sabatier, F.; Dignat-George, F. Extracellular Vesicles in Angiogenesis. Circ. Res. 2017, 120, 1658–1673. [Google Scholar] [CrossRef] [PubMed]
- Gehrmann, U.; Näslund, T.I.; Hiltbrunner, S.; Larssen, P.; Gabrielsson, S. Harnessing the exosome-induced immune response for cancer immunotherapy. Semin. Cancer Biol. 2014, 28, 58–67. [Google Scholar] [CrossRef] [PubMed]
- Kong, J.; Tian, H.; Zhang, F.; Zhang, Z.; Li, J.; Liu, X.; Li, X.; Liu, J.; Li, X.; Jin, D.; et al. Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts. Mol. Cancer 2019, 18, 175. [Google Scholar] [CrossRef] [PubMed]
- Zarà, M.; Guidetti, G.F.; Camera, M.; Canobbio, I.; Amadio, P.; Torti, M.; Tremoli, E.; Barbieri, S.S. Biology and Role of Extracellular Vesicles (EVs) in the Pathogenesis of Thrombosis. Int. J. Mol. Sci. 2019, 20, 2840. [Google Scholar] [CrossRef] [Green Version]
- Tannetta, D.; Dragovic, R.; Alyahyaei, Z.; Southcombe, J. Extracellular vesicles and reproduction–promotion of successful pregnancy. Cell. Mol. Immunol. 2014, 11, 548–563. [Google Scholar] [CrossRef] [Green Version]
- Rajendran, L.; Honsho, M.; Zahn, T.R.; Keller, P.; Geiger, K.D.; Verkade, P.; Simons, K. Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. USA 2006, 103, 11172–11177. [Google Scholar] [CrossRef] [Green Version]
- Riancho, J.; Vázquez-Higuera, J.L.; Pozueta, A.; Lage, C.; Kazimierczak, M.; Bravo, M.; Calero, M.; Gonalezález, A.; Rodríguez, E.; Lleó, A.; et al. MicroRNA Profile in Patients with Alzheimer’s Disease: Analysis of miR-9-5p and miR-598 in Raw and Exosome Enriched Cerebrospinal Fluid Samples. J. Alzheimer’s Dis. 2017, 57, 483–491. [Google Scholar] [CrossRef]
- Gregson, A.L.; Hoji, A.; Injean, P.; Poynter, S.T.; Briones, C.; Palchevskiy, V.; Sam Weigt, S.; Shino, M.Y.; Derhovanessian, A.; Sayah, D.; et al. Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection. Am. J. Respir. Crit. Care Med. 2015, 192, 1490–1503. [Google Scholar] [CrossRef] [Green Version]
- Musante, L.; Bontha, S.V.; La Salvia, S.; Fernandez-Piñeros, A.; Lannigan, J.; Le, T.H.; Mas, V.; Erdbrügger, U. Rigorous characterization of urinary extracellular vesicles (uEVs) in the low centrifugation pellet—A neglected source for uEVs. Sci. Rep. 2020, 10, 3701. [Google Scholar] [CrossRef]
- Allenson, K.; Castillo, J.; San Lucas, F.A.; Scelo, G.; Kim, D.U.; Bernard, V.; Davis, G.; Kumar, T.; Katz, M.; Overman, M.J.; et al. High prevalence of mutantKRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. Ann. Oncol. 2017, 28, 741–747. [Google Scholar] [CrossRef] [PubMed]
- Hur, J.Y.; Lee, J.S.; Kim, I.A.; Kim, H.J.; Kim, W.S.; Lee, K.Y. Extracellular vesicle-based EGFR genotyping in bronchoalveolar lavage fluid from treatment-naive non-small cell lung cancer patients. Transl. Lung Cancer Res. 2019, 8, 1051–1060. [Google Scholar] [CrossRef] [PubMed]
- García-Silva, S.; Miguel Gallardo, M.; Peinado, H. DNA-Loaded Extracellular Vesicles in Liquid Biopsy: Tiny Players With Big Potential? Front. Cell Dev. Bio. 2021, 8, 622579. [Google Scholar] [CrossRef] [PubMed]
- Möhrmann, L.; Huang, H.J.; Hong, D.S.; Tsimberidou, A.M.; Fu, S.; Piha-Paul, S.A.; Subbiah, V.; Karp, D.D.; Naing, A.; Krug, A.; et al. Liquid Biopsies Using Plasma Exosomal Nucleic Acids and Plasma Cell-Free DNA Compared with Clinical Outcomes of Patients with Advanced Cancers. Clin. Cancer Res. 2018, 24, 181–188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, W.; Hurley, J.J.; Roberts, D.; Chakrabortty, S.K.; Enderle, D.; Noerholm, M.; Breakefield, X.O.; Skog, J.K. Exosome-based liquid biopsies in cancer: Opportunities and challenges. Ann. Oncol. 2021, 32, 466–477. [Google Scholar] [CrossRef]
- Keller, S.; Ridinger, J.; Rupp, A.-K.; Janssen, J.W.; Altevogt, P. Body fluid derived exosomes as a novel template for clinical diagnostics. J. Transl. Med. 2011, 9, 86. [Google Scholar] [CrossRef] [Green Version]
- Montanari, M.; Rossetti, S.; Cavaliere, C.; D’Aniello, C.; Malzone, M.G.; Vanacore, D.; Di Franco, R.; Mantia, E.L.; Iovane, G.; Piscitelli, R.; et al. Epithelial-mesenchymal transition in prostate cancer: An overview. Oncotarget 2017, 8, 35376–35389. [Google Scholar] [CrossRef] [Green Version]
- Li, Y.; Li, Q.; Li, D.; Gu, J.; Qian, D.; Qin, X.; Chen, Y. Exosome carrying PSGR promotes stemness and epithelial-mesenchymal transition of low aggressive prostate cancer cells. Life Sci. 2021, 264, 118638. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Ye, L.; Zhang, X.; Wang, M.; Lin, C.; Huang, S.; Guo, W.; Lai, Y.; Du, H.; Li, J.; et al. FZD8, a target of p53, promotes bone metastasis in prostate cancer by activating canonical Wnt/β-catenin signaling. Cancer Lett. 2017, 402, 166–176. [Google Scholar] [CrossRef]
- Sandsmark, E.; Hansen, A.F.; Selnæs, K.M.; Bertilsson, H.; Bofin, A.M.; Wright, A.J.; Viset, T.; Richardsen, E.; Drabløs, F.; Bathen, T.F.; et al. A novel non-canonical Wnt signature for prostate cancer aggressiveness. Oncotarget 2017, 8, 9572–9586. [Google Scholar] [CrossRef]
- Acevedo, V.D.; Gangula, R.D.; Freeman, K.W.; Li, R.; Zhang, Y.; Wang, F.; Ayala, G.E.; Peterson, L.E.; Ittmann, M.; Spencer, D.M. Inducible FGFR-1 Activation Leads to Irreversible Prostate Adenocarcinoma and an Epithelial-to-Mesenchymal Transition. Cancer Cell 2007, 12, 559–571. [Google Scholar] [CrossRef] [Green Version]
- Perez-Hernandez, J.; Riffo-Campos, A.L.; Ortega, A.; Martinez-Arroyo, O.; Perez-Gil, D.; Olivares, D.; Solaz, E.; Martinez, F.; Martínez-Hervás, S.; Chaves, F.J.; et al. Urinary- and Plasma-Derived Exosomes Reveal a Distinct MicroRNA Signature Associated With Albuminuria in Hypertension. Hypertension 2021, 77, 960–971. [Google Scholar] [CrossRef]
- Conde-Vancells, J.; Rodriguez-Suarez, E.; Gonzalez, E.; Berisa, A.; Gil, D.; Embade, N.; Valle, M.; Luka, Z.; Elortza, F.; Wagner, C.; et al. Candidate biomarkers in exosome-like vesicles purified from rat and mouse urine samples. Proteom. Clin. Appl. 2010, 4, 416–425. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, X.; Kurywchak, P.; Wolf-Dennen, K.; Che, S.P.Y.; Sulakhe, D.; D’Souza, M.; Xie, B.; Maltsev, N.; Gilliam, T.C.; Wu, C.-C.; et al. Unique somatic variants in the DNA from urine exosomes of bladder cancer patients. Mol. Ther.-Methods Clin. Dev. 2021, 22, 360–376. [Google Scholar] [CrossRef]
- Krug, A.K.; Enderle, D.; Karlovich, C.; Priewasser, T.; Bentink, S.; Spiel, A.; Brinkmann, K.; Emenegger, J.; Grimm, D.G.; Castellanos-Rizaldos, E.; et al. Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma. Ann. Oncol. 2018, 29, 700–706. [Google Scholar] [CrossRef] [Green Version]
- Liu, Q.; Yu, Z.; Yuan, S.; Xie, W.; Li, C.; Hu, Z.; Xiang, Y.; Wu, N.; Wu, L.; Bai, L.; et al. Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer. Oncotarget 2017, 8, 13048–13058. [Google Scholar] [CrossRef] [Green Version]
- Tanaka, Y.; Kamohara, H.; Kinoshita, K.; Kurashige, J.; Ishimoto, T.; Iwatsuki, M.; Watanabe, M.; Baba, H. Clinical impact of serum exosomal microRNA-21 as a clinical biomarker in human esophageal squamous cell carcinoma. Cancer 2013, 119, 1159–1167. [Google Scholar] [CrossRef] [PubMed]
- Huang, X.; Yuan, T.; Liang, M.; Du, M.; Xia, S.; Dittmar, R. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur. Urol. 2015, 67, 33–41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhagirath, D.; Yang, T.L.; Bucay, N.; Sekhon, K.; Majid, S.; Shahryari, V.; Dahiya, R.; Tanaka, Y.; Saini, S. microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer. Cancer Res. 2018, 78, 1833–1844. [Google Scholar] [CrossRef] [Green Version]
- Guo, J.; Luo, C.; Yang, Y.; Dong, J.; Guo, Z.; Yang, J.; Lian, H.; Ye, C.; Liu, M. MiR-491-5p, as a Tumor Suppressor, Prevents Migration and Invasion of Breast Cancer by Targeting ZNF-703 to Regulate AKT/mTOR Pathway. Cancer Manag. Res. 2021, 13, 403–413. [Google Scholar] [CrossRef]
- Lu, L.; Cai, M.; Peng, M.; Wang, F.; Zhai, X. miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer. Cancer Manag. Res. 2019, 11, 1805–1816. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, Z.; Lü, Y.; Jiang, Q.; Yang, Y.; Dang, C.; Sun, R. miR-491 inhibits BGC-823 cell migration via targeting HMGA2. Int. J. Biol. Markers 2019, 34, 364–372. [Google Scholar] [CrossRef] [PubMed]
- Hu, S.; Wang, H.; Yan, D.; Lu, W.; Gao, P.; Lou, W.; Kong, X. Loss of miR-16 contributes to tumor progression by activation of tousled-like kinase 1 in oral squamous cell carcinoma. Cell Cycle 2018, 17, 2284–2295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gu, Z.; Li, Z.; Xu, R.; Zhu, X.; Hu, R.; Xue, Y.; Xu, W. miR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3. Front. Pharmacol. 2020, 11, 1324. [Google Scholar] [CrossRef] [PubMed]
- Huang, Z.; Chen, W.; Du, Y.; Guo, Q.; Mao, Y.; Zhou, X.; Hua, D. Serum miR-16 as a potential biomarker for human cancer diagnosis: Results from a large-scale population. J. Cancer Res. Clin. Oncol. 2019, 145, 787–796. [Google Scholar] [CrossRef]
- Bai, Y.; Zhao, H. Liquid biopsy in tumors: Opportunities and challenges. Ann. Transl. Med. 2018, 6, S89. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Herrero, C.; Ferreirós, A.; Pérez-Fentes, D.; León-Mateos, L.; López-López, R.; Abal, M.; Alonso-Alconada, L. Extracellular Vesicles’ Genetic Cargo as Noninvasive Biomarkers in Cancer: A Pilot Study Using ExoGAG Technology. Biomedicines 2023, 11, 404. https://doi.org/10.3390/biomedicines11020404
Herrero C, Ferreirós A, Pérez-Fentes D, León-Mateos L, López-López R, Abal M, Alonso-Alconada L. Extracellular Vesicles’ Genetic Cargo as Noninvasive Biomarkers in Cancer: A Pilot Study Using ExoGAG Technology. Biomedicines. 2023; 11(2):404. https://doi.org/10.3390/biomedicines11020404
Chicago/Turabian StyleHerrero, Carolina, Alba Ferreirós, Daniel Pérez-Fentes, Luis León-Mateos, Rafael López-López, Miguel Abal, and Lorena Alonso-Alconada. 2023. "Extracellular Vesicles’ Genetic Cargo as Noninvasive Biomarkers in Cancer: A Pilot Study Using ExoGAG Technology" Biomedicines 11, no. 2: 404. https://doi.org/10.3390/biomedicines11020404
APA StyleHerrero, C., Ferreirós, A., Pérez-Fentes, D., León-Mateos, L., López-López, R., Abal, M., & Alonso-Alconada, L. (2023). Extracellular Vesicles’ Genetic Cargo as Noninvasive Biomarkers in Cancer: A Pilot Study Using ExoGAG Technology. Biomedicines, 11(2), 404. https://doi.org/10.3390/biomedicines11020404