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Review

Emerging Role of Extracellular Vesicles in Biomarking the Gastrointestinal Diseases

, , &
Pages 939-962 | Received 28 Mar 2021, Accepted 09 Jul 2021, Published online: 25 Jul 2021

References

  • Heijnen HF, Schiel AE, Fijnheer R, et al. Activated Platelets Release Two Types of Membrane Vesicles: microvesicles by Surface Shedding and Exosomes Derived From Exocytosis of Multivesicular Bodies and-Granules. Blood. 1999;94(11):3791–3799.
  • Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol. 2009;19(2):43–51.
  • Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569.
  • Al-Nedawi K, Meehan B, Micallef J, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol. 2008;10(5):619.
  • Di Vizio D, Morello M, Dudley AC, et al. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am J Pathol. 2012;181(5):1573–1584.
  • Caby M-P, Lankar D, Vincendeau-Scherrer C, et al. Exosomal-like vesicles are present in human blood plasma. Int Immunol. 2005;17(7):879–887.
  • Pisitkun T, Shen R-F, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Nat Acad Sci. 2004;101(36):13368–13373.
  • Ogawa Y, Miura Y, Harazono A, et al. Proteomic analysis of two types of exosomes in human whole saliva. Biol Pharm Bull. 2011;34(1):13–23.
  • Asea A, Jean-Pierre C, Kaur P, et al. Heat shock protein-containing exosomes in mid-trimester amniotic fluids. J Reprod Immunol. 2008;79(1):12–17.
  • Admyre C, Johansson SM, Qazi KR, et al. Exosomes with immune modulatory features are present in human breast milk. J Immunol. 2007;179(3):1969–1978.
  • Ticlea M, Bratu LM, Bodog F, et al. The use of exosomes as biomarkers for evaluating and monitoring critically Ill polytrauma patients with sepsis. Biochem Genet. 2017;55(1):1–9.
  • Andre F, Schartz NE, Movassagh M, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360(9329):295–305.
  • Riancho J, Vázquez-Higuera JL, Pozueta 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 Alzheimers Dis. 2017;57(2):483–491.
  • Yang J-Y, Sun Y-W, Liu D-J, et al. MicroRNAs in stool samples as potential screening biomarkers for pancreatic ductal adenocarcinoma cancer. Am J Cancer Res. 2014;4(6):663.
  • Laulagnier K, Motta C, Hamdi S, et al. Mast cell-and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J. 2004;380(1):161–171. .
  • Zakharova L, Svetlova M, Fomina AF. T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. J Cell Physiol. 2007;212(1):174–181.
  • Xiang X, Poliakov A, Liu C, et al. Induction of myeloid‐derived suppressor cells by tumor exosomes. Int J Cancer. 2009;124(11):2621–2633.
  • Redzic JS, Balaj L, van der Vos KE, et al., Extracellular RNA mediates and marks cancer progression. Semin Cancer Biol. 2014;28:14-23. DOI:https://doi.org/10.1016/j.semcancer.2014.04.010.
  • Yokose T, Kabe Y, Matsuda A, et al. O-Glycan-Altered Extracellular Vesicles: a Specific Serum Marker Elevated in Pancreatic Cancer. Cancers (Basel). 2020;12(9):2469.
  • Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97(2):329–339.
  • Pan B-T, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33(3):967–978.
  • Valadi H, Ekström K, Bossios A, et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 9(6): 654. 2007.
  • Henne WM, Stenmark H, Emr SD. Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Biol. 2013;5(9):a016766.
  • Baietti MF, Zhang Z, Mortier E, et al. Syndecan–syntenin–ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012;14(7):677.
  • Ostrowski M, Carmo NB, Krumeich S, et al., Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 12(1): 19. 2010.
  • Sala-Valdés M, Ailane N, Greco C, et al. Targeting tetraspanins in cancer. Expert Opin Ther Targets. 2012;16(10):985–997.
  • Jankovičová J, Sečová P, Michalková K, et al. Tetraspanins, More than Markers of Extracellular Vesicles in Reproduction. Int J Mol Sci. 2020;21(20):7568.
  • Hemler ME. Specific tetraspanin functions. J Cell Biol. 2001;155(7):1103–1108.
  • Hemler ME. Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol. 2005;6(10):801–811.
  • Charrin S, Le Naour F, Silvie O, et al. Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J. 2009;420(2):133–154.
  • Berditchevski F. Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci. 2001;114(23):4143–4151.
  • Longo N, Yáñez-Mó M, Mittelbrunn M, et al. Regulatory role of tetraspanin CD9 in tumor–endothelial cell interaction during transendothelial invasion of melanoma cells. Blood J Am Soc Hematol. 2001;98(13):3717–3726.
  • Hemler ME. Targeting of tetraspanin proteins—potential benefits and strategies. Nat Rev Drug Discov. 2008;7(9):747–758.
  • van Spriel AB, Figdor CG. The role of tetraspanins in the pathogenesis of infectious diseases. Microbes Infect. 2010;12(2):106–112.
  • Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, et al. The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J Biol Chem. 2013;288(17):11649–11661.
  • Lin J, Li J, Huang B, et al. Exosomes: novel biomarkers for clinical diagnosis. Sci World J. 2015;2015:8. DOI:https://doi.org/10.1155/2015/657086
  • Van Niel G, Charrin S, Simoes S, et al. The tetraspanin CD63 regulates ESCRT-independent and-dependent endosomal sorting during melanogenesis. Dev Cell. 2011;21(4):708–721.
  • Edgar JR, Eden ER, Futter CE. Hrs‐and CD63‐dependent competing mechanisms make different sized endosomal intraluminal vesicles. Traffic. 2014;15(2):197–211.
  • Shekari F, Nazari A, Kashani SA, et al. Pre-clinical investigation of mesenchymal stromal cell-derived extracellular vesicles: a systematic review. Cytotherapy. 2021;23(4):277-284. DOI:https://doi.org/10.1016/j.jcyt.2020.12.009
  • Miki Y, Yashiro M, Okuno T, et al. Clinico-pathological significance of exosome marker CD63 expression on cancer cells and stromal cells in gastric cancer. PLoS One. 2018;13(9):e0202956.
  • GKP MK, Laurini JA, Bhardwaj A, et al. Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma. J Gastrointest Oncol. 2019;10(4):695.
  • Duijvesz D, Versluis CYL, Van Der Fels CA, et al. Immuno‐based detection of extracellular vesicles in urine as diagnostic marker for prostate cancer. Int J Cancer. 2015;137(12):2869–2878.
  • Mizutani K, Terazawa R, Kameyama K, et al. Isolation of prostate cancer-related exosomes. Anticancer Res. 2014;34(7):3419–3423.
  • Miki Y, Yashiro M, Okuno T, et al., CD9-positive exosomes from cancer-associated fibroblasts stimulate the migration ability of scirrhous-type gastric cancer cells. Br J Cancer. 118(6): 867–877. 2018.
  • Welker M-W, Reichert D, Susser S, et al. Soluble serum CD81 is elevated in patients with chronic hepatitis C and correlates with alanine aminotransferase serum activity. PloS One. 2012;7(2):e30796.
  • Li XB, Zhang ZR, Schluesener HJ, et al. Role of exosomes in immune regulation. J Cell Mol Med. 2006;10(2):364–375.
  • Peinado H, Alečković M, Lavotshkin S, et al., Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 18(6): 883. 2012.
  • Shimoda M, Principe S, Jackson HW, et al. Loss of the Timp gene family is sufficient for the acquisition of the CAF-like cell state. Nat Cell Biol. 2014;16(9):889.
  • Boelens MC, Wu TJ, Nabet BY, et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell. 2014;159(3):499–513.
  • Najminejad H, Kalantar SM, Abdollahpour‐Alitappeh M, et al. Emerging roles of exosomal miRNAs in breast cancer drug resistance. IUBMB Life. 2019;71(11):1672–1684.
  • Fong MY, Zhou W, Liu L, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015;17(2):183.
  • Ostenfeld MS, Jeppesen DK, Laurberg JR, et al. Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer Res. 2014;74(20):5758–5771.
  • Umezu T, Tadokoro H, Azuma K, et al. Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1. Blood. 2014;124(25):3748–3757.
  • Yaghoubi S, Najminejad H, Dabaghian M, et al. How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment? IUBMB Life. 2020;72(7):1286–1305.
  • Nedaeinia R, Manian M, Jazayeri M, et al. Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer. Cancer Gene Ther. 2017;24(2):48.
  • Ailawadi S, Wang X, Gu H, et al. Pathologic function and therapeutic potential of exosomes in cardiovascular disease. Biochim Biophys Acta Mol Basis Dis. 2015;1852(1):1–11.
  • Yáñez-Mó M, Siljander PR-M, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4(1):27066.
  • Böing AN, Van Der Pol E, Grootemaat AE, et al. Single-step isolation of extracellular vesicles by size-exclusion chromatography. J Extracell Vesicles. 2014;3(1):23430.
  • Théry C, Witwer KW, Aikawa E, 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(1):1535750.
  • Li P, Kaslan M, Lee SH, et al. Progress in exosome isolation techniques. Theranostics. 2017;7(3):789.
  • Angelini F, Ionta V, Rossi F, et al. Exosomes isolation protocols: facts and artifacts for cardiac regeneration. Front Biosci (Schol Ed). 2016;8(2):303–311.
  • Coumans FA, Brisson AR, Buzas EI, et al. Methodological guidelines to study extracellular vesicles. Circ Res. 2017;120(10):1632–1648.
  • Kowal J, Arras G, Colombo M, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Nat Acad Sci. 2016;113(8):E968–E977.
  • Bu H, He D, He X, et al. Exosomes: isolation, analysis, and applications in cancer detection and therapy. Chembiochem. 2019;20(4):451–461.
  • Nordin JZ, Lee Y, Vader P, et al. Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties. Nanomedicine. 2015;11(4):879–883.
  • Hong C-S, Funk S, Muller L, et al. Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer. J Extracell Vesicles. 2016;5(1):29289.
  • Liu C, Guo J, Tian F, et al. Field-free isolation of exosomes from extracellular vesicles by microfluidic viscoelastic flows. ACS Nano. 2017;11(7):6968–6976.
  • Batrakova EV, Kim MS. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. 2015;219:396–405.
  • Albertsson P-Å, Frick G. Partition of virus particles in a liquid two-phase system. Biochim Biophys Acta. 1960;37(2):230–237.
  • Rider MA, Hurwitz SN, Meckes JDG. ExtraPEG: a polyethylene glycol-based method for enrichment of extracellular vesicles. Sci Rep. 2016;6(1):23978.
  • Lee Y, El Andaloussi S, Wood MJ. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet. 2012;21(R1):R125–R134.
  • Tauro BJ, Greening DW, Mathias RA, et al., Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods. 56(2): 293–304. 2012.
  • Tauro BJ, Greening DW, Mathias RA, et al. Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol Cell Proteomics. 2013;12(3):587–598.
  • Soo CY, Song Y, Zheng Y, et al. Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells. Immunology. 2012;136(2):192–197.
  • Van der Pol E, Coumans F, Grootemaat A, et al. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost. 2014;12(7):1182–1192.
  • Paktinat S, Hashemi SM, Novin MG, et al. Seminal exosomes induce interleukin-6 and interleukin-8 secretion by human endometrial stromal cells. Eur J Obstetrics Gynecol Reprod Biol. 2019;235:71–76.
  • Arraud N, Linares R, Tan S, et al. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J Thromb Haemost. 2014;12(5):614–627.
  • Szatanek R, Baj-Krzyworzeka M, Zimoch J, et al. The methods of choice for extracellular vesicles (EVs) characterization. Int J Mol Sci. 2017;18(6):1153.
  • Bhat A, Sharma A, Bharti AC. Upstream Hedgehog signaling components are exported in exosomes of cervical cancer cell lines. Nanomedicine. 2018;13(17):2127–2138.
  • Kenari AN, Kastaniegaard K, Greening DW, et al. Exosome‐mimetic nanovesicles contain distinct proteome and post‐translational modified protein cargo, in comparison to exosomes. Proteomics. 2019;19(8):1800161.
  • An T, Qin S, Xu Y, et al. Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J Extracell Vesicles. 2015;4(1):27522.
  • Skog J, Würdinger T, Van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470. .
  • Tang Y-T, Huang -Y-Y, Zheng L, et al. Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum. Int J Mol Med. 2017;40(3):834–844.
  • Eldh M, Lötvall J, Malmhäll C, et al. Importance of RNA isolation methods for analysis of exosomal RNA: evaluation of different methods. Mol Immunol. 2012;50(4):278–286.
  • Taylor DD, Zacharias W, Gercel-Taylor C. Exosome isolation for proteomic analyses and RNA profiling. In: Simpson R., Greening D. editors. Serum/Plasma proteomics. Methods in molecular biology (Methods and Protocols), vol 728. Humana Press; 2011. https://doi.org/10.1007/978-1-61779-068-3_15
  • Mateescu B, Kowal EJ, van Balkom BW, et al. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA–an ISEV position paper. J Extracell Vesicles. 2017;6(1):1286095.
  • Kim J, Tan Z, Lubman DM. Exosome enrichment of human serum using multiple cycles of centrifugation. Electrophoresis. 2015;36(17):2017–2026.
  • Washburn MP, Wolters D, Yates III JR. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol. 2001;19(3):242.
  • Blackstock WP, Weir MP. Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol. 1999;17(3):121–127.
  • Lange V, Picotti P, Domon B, et al. Selected reaction monitoring for quantitative proteomics: a tutorial. Mol Syst Biol. 2008;4(1):222.
  • Peterson AC, Russell JD, Bailey DJ, et al. Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics. Mol Cell Proteomics. 2012;11(11):1475–1488.
  • Mathivanan S, Simpson RJ. ExoCarta: a compendium of exosomal proteins and RNA. Proteomics. 2009;9(21):4997–5000.
  • Kalra H, Simpson RJ, Ji H, et al. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012;10(12):e1001450.
  • Kim D-K, Lee J, Kim SR, et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics. 2014;31(6):933–939.
  • Zuo L, Tao H, Xu H, et al. Exosomes-Coated miR-34a Displays Potent Antitumor Activity in Pancreatic Cancer Both in vitro and in vivo. Drug Des Devel Ther. 2020;14:3495.
  • Lai A, Kinhal V, Nuzhat Z, et al. Proteomics Method to Identification of Protein Profiles in Exosomes. In: Murthi P., Vaillancourt C. K, editors. Preeclampsia. Methods in Molecular Biology, vol 1710. New York, NY: Humana Press; 2018. https://doi.org/10.1007/978-1-4939-7498-6_11: .
  • Wang Y-T, Shi T, Srivastava S, et al. Proteomic Analysis of Exosomes for Discovery of Protein Biomarkers for Prostate and Bladder Cancer. Cancers (Basel). 2020;12(9):2335. .
  • Jeddi F, Soozangar N, Sadeghi MR, et al. Nrf2 overexpression is associated with P-glycoprotein upregulation in gastric cancer. Biomed Pharmacother. 2018;97:286–292.
  • Smyth E, Verheij M, Allum W, et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl_5):v38–v49.
  • Yan Y, Fu G, Ye Y, et al. Exosomes participate in the carcinogenesis and the malignant behavior of gastric cancer. Scand J Gastroenterol. 2017;52(5):499–504.
  • Orditura M, Galizia G, Sforza V, et al. Treatment of gastric cancer. World J Gastroenterol. 2014;20(7):1635.
  • Maia J, Caja S, Strano Moraes MC, et al. Exosome-based cell-cell communication in the tumor microenvironment. Front Cell Dev Biol. 2018;6:18.
  • Yang H, Zhang H, Ge S, et al. Exosome-derived miR-130a activates angiogenesis in gastric Cancer by targeting C-MYB in vascular endothelial cells. Mol Ther. 2018;26(10):2466–2475.
  • Li W, Gao Y-Q. MiR-217 is involved in the carcinogenesis of gastric cancer by down-regulating CDH1 expression. Kaohsiung J Med Sci. 2018;34(7):377–384.
  • Huang Z, Zhu D, Wu L, et al. Six serum-based miRNAs as potential diagnostic biomarkers for gastric cancer. Cancer Epidemiol Prev Biomarkers. 2017;26(2):188–196.
  • George G, Mittal RD. MicroRNAs: potential biomarkers in cancer. Indian J Clin Biochem. 2010;25(1):4–14.
  • Tazawa H, Nagasaka T, Kagawa S, et al. MicroRNA as a molecular target for gastrointestinal cancers. Trans Gastrointest Cancer. 2015;4(3):219–235.
  • Wang X, Zhang H, Bai M, et al. Exosomes serve as nanoparticles to deliver anti-miR-214 to reverse chemoresistance to cisplatin in gastric cancer. Mol Ther. 2018;26(3):774–783.
  • Wang N, Wang L, Yang Y, et al. A serum exosomal microRNA panel as a potential biomarker test for gastric cancer. Biochem Biophys Res Commun. 2017;493(3):1322–1328.
  • Ren J, Zhou Q, Li H, et al. Characterization of exosomal RNAs derived from human gastric cancer cells by deep sequencing. Tumor Biol. 2017;39(4):1010428317695012.
  • Li B-S, Zhao Y, Guo G, et al. Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for gastric cancer detection. PloS One. 2012;7(7):e41629.
  • Imamura T, Komatsu S, Ichikawa D, et al. Low plasma levels of miR-101 are associated with tumor progression in gastric cancer. Oncotarget. 2017;8(63):106538.
  • Kumata Y, Iinuma H, Suzuki Y, et al. Exosome‑encapsulated microRNA‑23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage. Oncol Rep. 2018;40(1):319–330.
  • Suzuki H, Yamamoto E, Nojima M, et al. Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect. Carcinogenesis. 2010;31(12):2066–2073.
  • Kim K, Lee H-C, Park J-L, et al. Epigenetic regulation of microRNA-10b and targeting of oncogenic MAPRE1 in gastric cancer. Epigenetics. 2011;6(6):740–751.
  • Tang S, Cheng J, Yao Y, et al. Combination of Four Serum Exosomal MiRNAs as Novel Diagnostic Biomarkers for Early-Stage Gastric Cancer. Front Genet. 2020;11:237.
  • Ming S-C. Cellular and molecular pathology of gastric carcinoma and precursor lesions: a critical review. Gastric Cancer. 1998;1(1):31–50.
  • Sugano K. Screening of gastric cancer in Asia. Best Pract Res Clin Gastroenterol. 2015;29(6):895–905.
  • Liu H, Li P-W, Yang W-Q, et al. Identification of non-invasive biomarkers for chronic atrophic gastritis from serum exosomal microRNAs. BMC Cancer. 2019;19(1):129.
  • Polakovicova I, Jerez S, Wichmann IA, et al. Role of microRNAs and exosomes in Helicobacter pylori and Epstein-Barr virus associated gastric cancers. Front Microbiol. 2018;9:636.
  • Meckes DG, Shair KH, Marquitz AR, et al. Human tumor virus utilizes exosomes for intercellular communication. Proc Nat Acad Sci. 2010;107(47):20370–20375.
  • Shimoda A, Ueda K, Nishiumi S, et al. Exosomes as nanocarriers for systemic delivery of the Helicobacter pylori virulence factor CagA. Sci Rep. 2016;6(1):1–9.
  • Yao Y, Wu J, Gu T, et al. Comparative analysis of the interaction of HSPs in dendritic cells, macrophages, RGM-1 cells infected by Helicobacter pylori. Am J Transl Res. 2016;8(10):4184.
  • Yamamoto H, Watanabe Y, Oikawa R, et al. BARHL2 methylation using gastric wash DNA or gastric juice exosomal DNA is a useful marker for early detection of gastric cancer in an H-pylori-independent manner. Clin Trans Gastroenterol. 2016;7(7):e184.
  • Yoon JH, Ham I-H, Kim O, et al. Gastrokine 1 protein is a potential theragnostic target for gastric cancer. Gastric Cancer. 2018;21(6):956–967.
  • Anami K, Oue N, Noguchi T, et al. TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer. Gastric Cancer. 2016;19(2):370–380.
  • Fu H, Yang H, Zhang X, et al. Exosomal TRIM3 is a novel marker and therapy target for gastric cancer. J Exp Clin Cancer Res. 2018;37(1):162.
  • Yang H, Fu H, Wang B, et al. Exosomal miR‐423‐5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer. Mol Carcinog. 2018;57(9):1223–1236.
  • Hu Y, Qi C, Liu X, et al. Malignant ascites-derived exosomes promote peritoneal tumor cell dissemination and reveal a distinct miRNA signature in advanced gastric cancer. Cancer Lett. 2019;457:142–150.
  • Tokuhisa M, Ichikawa Y, Kosaka N, et al. Exosomal miRNAs from peritoneum lavage fluid as potential prognostic biomarkers of peritoneal metastasis in gastric cancer. PloS One. 2015;10(7):e0130472.
  • Arita T, Ichikawa D, Konishi H, et al. Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells. Oncotarget. 2016;7(35):56855.
  • Chen KB, Chen J, Jin XL, et al. Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications. Biomed Rep. 2018;8(6):503–509.
  • Ohshima K, Inoue K, Fujiwara A, et al. Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cancer cell line. PloS One. 2010;5(10):e13247.
  • Gonzalez DM, Medici D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal. 2014;7(344):re8–re8.
  • Yen E-Y, Miaw S-C, Yu J-S, et al. Exosomal TGF-β1 is correlated with lymphatic metastasis of gastric cancers. Am J Cancer Res. 2017;7(11):2199.
  • Fan Y, Che X, Qu J, et al. Exosomal PD-L1 Retains Immunosuppressive Activity and is Associated with Gastric Cancer Prognosis. Ann Surg Oncol. 2019;26(11):3745–3755. DOI:https://doi.org/10.1245/s10434-019-07431-7
  • Zhang H, Deng T, Liu R, et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat Commun. 2017;8:15016.
  • GE4GAC group. Genomics and epidemiology for gastric adenocarcinomas. Appl Cancer Res. 2017;37:7. https://doi.org/10.1186/s41241-017-0011-2
  • Baran J, Baj-Krzyworzeka M, Weglarczyk K, et al. Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother. 2010;59(6):841–850.
  • Lin L-Y, Yang L, Zeng Q, et al. Tumor-originated exosomal lncUEGC1 as a circulating biomarker for early-stage gastric cancer. Mol Cancer. 2018;17(1):84.
  • Zhang X, Liang W, Liu J, et al. Long non-coding RNA UFC1 promotes gastric cancer progression by regulating miR-498/Lin28b. J Exp Clin Cancer Res. 2018;37(1):134.
  • Piao H-Y, Guo S, Wang Y, et al. Exosomal Long Non-Coding RNA CEBPA-AS1 Inhibits Tumor Apoptosis and Functions as a Non-Invasive Biomarker for Diagnosis of Gastric Cancer. Onco Targets Ther. 2020;13:1365.
  • Pan L, Liang W, Fu M, et al. Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression. J Cancer Res Clin Oncol. 2017;143(6):991–1004.
  • Li Q, Shao Y, Zhang X, et al. Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumor Biol. 2015;36(3):2007–2012.
  • Zhao R, Zhang Y, Zhang X, et al. Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer. Mol Cancer. 2018;17(1):68.
  • Saif MW. Pancreatic neoplasm in 2011: an update. J. Pancreas. 2011;12(4):316–321.
  • Moutinho-Ribeiro P, Macedo G, Melo SA. Pancreatic cancer diagnosis and management: has the time come to Prick the Bubble? Front. Endocrinol. 2019;9:779. DOI:https://doi.org/10.3389/fendo.2018.00779
  • Aikawa T, Whipple CA, Lopez ME, et al. Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells. J Clin Invest. 2008;118(1):89–99.
  • Melo SA, Luecke LB, Kahlert C, et al., Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 523(7559): 177. 2015.
  • Lai X, Wang M, McElyea SD, et al. A microRNA signature in circulating exosomes is superior to exosomal glypican-1 levels for diagnosing pancreatic cancer. Cancer Lett. 2017;393:86–93.
  • Castillo J, Bernard V, San Lucas F, et al. Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients. Ann Oncol. 2017;29(1):223–229.
  • Yang S, Che SP, Kurywchak P, 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(3):158–165.
  • Costa-Silva B, Aiello NM, Ocean AJ, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17(6):816.
  • Wang X, Luo G, Zhang K, et al. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Cancer Res. 2018;78(16):4586–4598.
  • Li J, Li Z, Jiang P, et al. Circular RNA IARS (circ-IARS) secreted by pancreatic cancer cells and located within exosomes regulates endothelial monolayer permeability to promote tumor metastasis. J Exp Clin Cancer Res. 2018;37(1):177.
  • Jin H, Liu P, Wu Y, et al. Exosomal zinc transporter ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer. Cancer Sci. 2018;109(9):2946.
  • Wei Q, Wei L, Zhang J, et al. EphA2‑enriched exosomes promote cell migration and are a potential diagnostic serum marker in pancreatic cancer. Mol Med Rep. 2020;22(4):2941–2947.
  • Wei Q, Zhang J, Li Z, et al. Serum Exo-EphA2 as a Potential Diagnostic Biomarker for Pancreatic Cancer. Pancreas. 2020;49(9):1213–1219.
  • Que R, Ding G, Chen J, et al. Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma. World J Surg Oncol. 2013;11(1):219.
  • Goto T, Fujiya M, Konishi H, et al. An elevated expression of serum exosomal microRNA-191,− 21,− 451a of pancreatic neoplasm is considered to be efficient diagnostic marker. BMC Cancer. 2018;18(1):116.
  • Li Z, Tao Y, Wang X, et al. Tumor-secreted exosomal miR-222 promotes tumor progression via regulating P27 expression and re-localization in pancreatic Cancer. Cell Physiol Biochem. 2018;51(2):610–629.
  • Qiu M, Hu J, Yang D, et al. Pattern of distant metastases in colorectal cancer: a SEER based study. Oncotarget. 2015;6(36):38658.
  • Rahib L, Smith BD, Aizenberg R. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–2921. DOI:https://doi.org/10.1158/0008-5472.CAN-14-0155
  • Ogata-Kawata H, Izumiya M, Kurioka D, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PloS One. 2014;9(4):e92921.
  • Hoshino A, Costa-Silva B, Shen T-L, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329.
  • Desmond BJ, Dennett ER, Danielson KM. Circulating Extracellular Vesicle MicroRNA as Diagnostic Biomarkers in Early Colorectal Cancer—A Review. Cancers (Basel). 2020;12(1):52.
  • Yan S, Han B, Gao S, et al. Exosome-encapsulated microRNAs as circulating biomarkers for colorectal cancer. Oncotarget. 2017;8(36):60149.
  • Peng ZY, Gu RH, Yan B. Downregulation of exosome‐encapsulated miR‐548c‐5p is associated with poor prognosis in colorectal cancer. J Cell Biochem. 2019;120(2):1457–1463.
  • Lai X, Friedman A. Exosomal microRNA concentrations in colorectal cancer: a mathematical model. J Theor Biol. 2017;415:70–83.
  • Karimi N, Feizi MAH, Safaralizadeh R, et al. Serum overexpression of miR-301a and miR-23a in patients with colorectal cancer. J Chin Med Assoc. 2019;82(3):215–220.
  • Matsumura T, Sugimachi K, Iinuma H, et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer. 2015;113(2):275.
  • Teng Y, Ren Y, Hu X, et al. MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression. Nat Commun. 2017;8(1):14448.
  • Liu X, Pan B, Sun L, et al. Circulating exosomal miR-27a and miR-130a act as novel diagnostic and prognostic biomarkers of colorectal cancer. Cancer Epidemiol Prev Biomarkers. 2018;27(7):746–754.
  • Beckler MD, Higginbotham JN, Franklin JL, et al. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol Cell Proteomics. 2013;12(2):343–355.
  • Cha DJ, Franklin JL, Dou Y, et al. KRAS-dependent sorting of miRNA to exosomes. Elife. 2015;4:e07197.
  • Dou Y, Cha DJ, Franklin JL, et al. Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes. Sci Rep. 2016;6(1):37982.
  • Wang Y, Mo Y, Gong Z, et al. Circular RNAs in human cancer. Mol Cancer. 2017;16(1):25. .
  • Cocquerelle C, Mascrez B, Hétuin D, et al. Mis‐splicing yields circular RNA molecules. FASEB J. 1993;7(1):155–160.
  • Zhang Y, Zhang X-O, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell. 2013;51(6):792–806.
  • Xie Y, Li J, Li P, et al. RNA-Seq Profiling of Serum Exosomal Circular RNAs Reveals Circ-PNN as a Potential Biomarker for Human Colorectal Cancer. Front Oncol. 2020;10:982.
  • Sun Y, Zheng W, Guo Z, et al. A novel TP53 pathway influences the HGS-mediated exosome formation in colorectal cancer. Sci Rep. 2016;6(1):28083.
  • Chen Y, Xie Y, Xu L, et al., Protein content and functional characteristics of serum‐purified exosomes from patients with colorectal cancer revealed by quantitative proteomics. Int J Cancer. 140(4): 900–913. 2017.
  • Cappello F, Marino Gammazza A, Palumbo Piccionello A, et al. Hsp60 chaperonopathies and chaperonotherapy: targets and agents. Expert Opin Ther Targets. 2014;18(2):185–208.
  • Campanella C, Rappa F, Sciumè C, et al. Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery. Cancer. 2015;121(18):3230–3239.
  • Valenti R, Huber V, Iero M, et al. Tumor-released microvesicles as vehicles of immunosuppression. Cancer Res. 2007;67(7):2912–2915.
  • Liu T, Zhang X, Gao S, et al. Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer. Oncotarget. 2016;7(51):85551.
  • Sachar DB, Walfish A. Inflammatory bowel disease: one or two diseases? Curr Gastroenterol Rep. 2013;15(1):298.
  • Bousvaros A, Antonioli D, Colletti R, et al. Differentiating ulcerative colitis from Crohn's disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007;44(5):653–674.
  • Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369(9573):1641–1657.
  • Stange EF, Travis SPL, Vermeire S, et al. European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut. 2006;55(suppl 1):i1–i15.
  • Plevy S, Silverberg MS, Lockton S, et al. Combined serological, genetic, and inflammatory markers differentiate non-IBD, Crohn’s disease, and ulcerative colitis patients. Inflamm Bowel Dis. 2013;19(6):1139–1148.
  • Tesija Kuna A. Serological markers of inflammatory bowel disease. Biochem Med. 2013;23(1):28–42.
  • Mokrowiecka A, Daniel P, Slomka M, et al. Clinical utility of serological markers in inflammatory bowel disease. Hepatogastroenterology. 2009;56(89):162–166.
  • Ponder A, Long MD. A clinical review of recent findings in the epidemiology of inflammatory bowel disease. Clin Epidemiol. 2013;5:237.
  • Elli L, Ciulla MM, Busca G, et al. Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease. Lab Invest. 2011;91(3):452.
  • Zhang H, Wang L, Li C, et al. Exosome-induced regulation in inflammatory bowel disease. Front Immunol. 2019;10:1464. DOI:https://doi.org/10.3389/fimmu.2019.01464.
  • Feagins LA, Souza RF, Spechler SJ. Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer. Nat Clin Pract Gastroenterol Hepatol. 2009;6(5):297–305.
  • Terzic J, Grivennikov S, Karin E, et al. Inflammation and colon cancer. Gastroenterol. 2010;138(6):2101–2114.e5.
  • Billiet T, Rutgeerts P, Ferrante M, et al. Targeting TNF-α for the treatment of inflammatory bowel disease. Expert Opin Biol Ther. 2014;14(1):75–101.
  • De Toro J, Herschlik L, Waldner C, et al. Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front Immunol. 2015;6:203.
  • Kayama H, Takeda K. Regulation of intestinal homeostasis by innate and adaptive immunity. Int Immunol. 2012;24(11):673–680.
  • van Lierop PP, Samsom JN, Escher JC, et al. Role of the innate immune system in the pathogenesis of inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2009;48(2):142–151.
  • Wong WY, Lee MML, Chan BD, et al. Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages. Proteomics. 2016;16(7):1131–1145.
  • Mitsuhashi S, Feldbrügge L, Csizmadia E, et al. Luminal extracellular vesicles (EVs) in inflammatory bowel disease (IBD) exhibit proinflammatory effects on epithelial cells and macrophages. Inflamm Bowel Dis. 2016;22(7):1587–1595.
  • Zheng X, Chen F, Zhang Q, et al., Salivary exosomal PSMA7: a promising biomarker of inflammatory bowel disease. Protein Cell. 8(9): 686–695. 2017.
  • Zhang X, Deeke SA, Ning Z, et al., Metaproteomics reveals associations between microbiome and intestinal extracellular vesicle proteins in pediatric inflammatory bowel disease. Nat Commun. 9(1): 2873. 2018.
  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
  • El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264–1273. e1.
  • Li C, Xu X. Biological functions and clinical applications of exosomal non-coding RNAs in hepatocellular carcinoma. Cell Mol Life Sci. 2019;76:4203–4219. https://doi.org/10.1007/s00018-019-03215-0.
  • Liu W-H, Ren L-N, Wang X, et al. Combination of exosomes and circulating microRNAs may serve as a promising tumor marker complementary to alpha-fetoprotein for early-stage hepatocellular carcinoma diagnosis in rats. J Cancer Res Clin Oncol. 2015;141(10):1767–1778.
  • Wang H, Hou L, Li A, et al. Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma. In: BioMed research international. 2014. p. 2014.
  • Lee YR, Kim G, Tak WY, et al. Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma. Int J Cancer. 2019;144(6):1444–1452.
  • Sohn W, Kim J, Kang SH, et al. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med. 2015;47(9):e184.
  • Cui Y, Xu H-F, Liu M-Y, et al. Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value. World J Gastroenterol. 2019;25(15):1890.
  • Liu W, Hu J, Zhou K, et al. Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma. Onco Targets Ther. 2017;10:3843.
  • Xue X, Zhao Y, Wang X, et al. Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma. J Cell Biochem. 2019;120(1):135–142.
  • Xue X, Wang X, Zhao Y, et al. Exosomal miR-93 promotes proliferation and invasion in hepatocellular carcinoma by directly inhibiting TIMP2/TP53INP1/CDKN1A. Biochem Biophys Res Commun. 2018;502(4):515–521.
  • Shi M, Jiang Y, Yang L, et al. Decreased levels of serum exosomal miR‐638 predict poor prognosis in hepatocellular carcinoma. J Cell Biochem. 2018;119(6):4711–4716.
  • Qu Z, Wu J, Wu J, et al. Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis. Oncotarget. 2017;8(46):80666.
  • Fang JH, Zhang ZJ, Shang LR, et al. Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins. Hepatology. 2018;68(4):1459–1475.
  • Matsuura Y, Wada H, Eguchi H, et al. Exosomal miR-155 Derived from Hepatocellular Carcinoma Cells Under Hypoxia Promotes Angiogenesis in Endothelial Cells. Dig Dis Sci. 2019;64(3):792–802.
  • Sugimachi K, Matsumura T, Hirata H, et al. Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation. Br J Cancer. 2015;112(3):532.
  • Nakano T, Chen IH, Wang CC, et al. Circulating exosomal miR‐92b: its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence. Am J Transplant. 2019;19(12):3250–3262.
  • Zhang C, Yang X, Qi Q, et al. lncRNA-HEIH in serum and exosomes as a potential biomarker in the HCV-related hepatocellular carcinoma. Cancer Biomarkers. 2018;21(3):651–659.
  • Xu H, Chen Y, Dong X, et al. Serum exosomal long noncoding RNAs ENSG00000258332. 1 and LINC00635 for the diagnosis and prognosis of hepatocellular carcinoma. Cancer Epidemiol Prev Biomarkers. 2018;27(6):710–716.
  • Li B, Mao R, Liu C, et al. LncRNA FAL1 promotes cell proliferation and migration by acting as a CeRNA of miR-1236 in hepatocellular carcinoma cells. Life Sci. 2018;197:122–129.
  • Sun L, Su Y, Liu X, et al. Serum and exosome long non coding RNAs as potential biomarkers for hepatocellular carcinoma. J Cancer. 2018;9(15):2631.
  • Gramantieri L, Baglioni M, Fornari F, et al. LncRNAs as novel players in hepatocellular carcinoma recurrence. Oncotarget. 2018;9(80):35085.
  • Zhu L, Li J, Gong Y, et al. Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis. Mol Cancer. 2019;18(1):74.
  • Wang G, Liu W, Zou Y, et al. Three isoforms of exosomal circPTGR1 promote hepatocellular carcinoma metastasis via the miR449a–MET pathway. EBioMedicine. 2019;40:432–445.
  • Xu H, Dong X, Chen Y, et al. Serum exosomal hnRNPH1 mRNA as a novel marker for hepatocellular carcinoma. Clin Chem Lab Med. 2018;56(3):479–484.
  • Sasaki K, Kohgo Y, Ohtake T. Splicing variant of hepcidin mRNA. Vitam Horm. 2019;110:131–141.
  • Abd El Gwad A, Matboli M, El‐Tawdi A, et al. Role of exosomal competing endogenous RNA in patients with hepatocellular carcinoma. J Cell Biochem. 2018;119(10):8600–8610. .
  • Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.
  • Kandiah K, Chedgy FJ, Subramaniam S, et al. Early squamous neoplasia of the esophagus: the endoscopic approach to diagnosis and management. Saudi J Gastroenterol. 2017;23(2):75.
  • Sunpaweravong S, Puttawibul P, Sunpaweravong P, et al. Correlation between Serum SCCA and CYFRA 2 1-1, Tissue Ki-67, and clinicopathological factors in patients with esophageal squamous cell carcinoma. J Med Assoc Thai. 2016;99(3):331–337.
  • Yan L, Dong X, Gao J, et al. A novel rapid quantitative method reveals stathmin‐1 as a promising marker for esophageal squamous cell carcinoma. Cancer Med. 2018;7(5):1802–1813.
  • Liu MX, Juan L, Ming X, et al. miR-93-5p transferred by exosomes promotes the proliferation of esophageal Cancer cells via intercellular communication by targeting PTEN. Biomedical and Environmental Sciences. 2018;31(3):171–185.
  • Zhou X, Wen W, Zhu J, et al. A six-microRNA signature in plasma was identified as a potential biomarker in diagnosis of esophageal squamous cell carcinoma. Oncotarget. 2017;8(21):34468.
  • Tanaka Y, Kamohara H, Kinoshita K, et al. Clinical impact of serum exosomal microRNA‐21 as a clinical biomarker in human esophageal squamous cell carcinoma. Cancer. 2013;119(6):1159–1167.
  • Liao J, Liu R, Shi Y-J, et al. Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting PDCD4 in esophageal cancer. Int J Oncol. 2016;48(6):2567–2579.
  • Chiam K, Wang T, Watson DI, et al. Circulating serum exosomal miRNAs as potential biomarkers for esophageal adenocarcinoma. J Gastrointestinal Surg. 2015;19(7):1208–1215.
  • Warnecke-Eberz U, Chon S-H, Hölscher AH, et al. Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor. Tumor Biol. 2015;36(6):4643–4653.
  • Zhang H, Lin W, Kannan K, et al. Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma. Oncotarget. 2013;4(11):2135.
  • Lin Y, Dong H, Deng W, et al. Evaluation of salivary exosomal chimeric GOLM1-NAA35 RNA as a potential biomarker in esophageal carcinoma. Clin Cancer Res. 2019;25(10):3035–3045.
  • Buscail E, Alix-Panabières C, Quincy P, et al. High clinical value of liquid biopsy to detect circulating tumor cells and tumor exosomes in pancreatic ductal adenocarcinoma patients eligible for up-front surgery. Cancers (Basel). 2019;11(11):1656.

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