Home Exosomal non-coding RNAs: a promising cancer biomarker
Article
Licensed
Unlicensed Requires Authentication

Exosomal non-coding RNAs: a promising cancer biomarker

  • Huan Yang , Hailong Fu , Wenrong Xu EMAIL logo and Xu Zhang EMAIL logo
Published/Copyright: May 11, 2016
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 12

Abstract

Novel and non-invasive biomarkers are urgently needed for early detection of cancer. Exosomes are nano-sized particles released by cells and contain various bioactive molecules including proteins, DNA, mRNAs, and non-coding RNAs. Increasing evidence suggests that exosomes play critical roles in tumorigenesis, tumor growth, metastasis, and therapy resistance. Exosomes could be readily accessible in nearly all the body fluids. The altered production of exosomes and aberrant expression of exosomal contents could reflect the pathological state of the body, indicating that exosomes and exosomal contents can be utilized as novel cancer biomarkers. Herein, we review the basic properties of exosomes, the functional roles of exosomes in cancer, and the methods of detecting exosomes and exosomal contents. In particular, we highlight the clinical values of exosomal non-coding RNAs in cancer diagnosis and prognosis.

Keywords: biomarker; cancer; exosomes; non-coding RNAs

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 81572075

Funding statement: This work was supported by the National Natural Science Foundation of China (Grant No. 81572075), the Innovation Project for Graduate Student Research of Jiangsu Province (Grant No. KYLX_1075), Jiangsu Key Laboratory of Medical Science and Laboratory Medicine (Grant No. JSKLM-2014-004), Jiangsu Province for Outstanding Sci-tech Innovation Team in Colleges and Universities (Grant No. SJK2013-10), and Jiangsu Province’s Outstanding Medical Academic Leader and Sci-tech Innovation Team Program (Grant No. LJ201117).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81572075), the Innovation Project for Graduate Student Research of Jiangsu Province (Grant No. KYLX_1075), Jiangsu Key Laboratory of Medical Science and Laboratory Medicine (Grant No. JSKLM-2014-004), Jiangsu Province for Outstanding Sci-tech Innovation Team in Colleges and Universities (Grant No. SJK2013-10), and Jiangsu Province’s Outstanding Medical Academic Leader and Sci-tech Innovation Team Program (Grant No. LJ201117).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Melo SA, Sugimoto H, O’Connell JT, Kato N, Villanueva A, Vidal A, et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 2014;26:707–21.10.1016/j.ccell.2014.09.005Search in Google Scholar

2. Nazarenko I, Rana S, Baumann A, McAlear J, Hellwig A, Trendelenburg M, et al. Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 2010;70:1668–78.10.1158/0008-5472.CAN-09-2470Search in Google Scholar

3. Zhang X, Yuan X, Shi H, Wu L, Qian H, Xu W. Exosomes in cancer: small particle, big player. J Hematol Oncol 2015;8:83.10.1186/s13045-015-0181-xSearch in Google Scholar

4. Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 2015;25:981–4.10.1038/cr.2015.82Search in Google Scholar

5. Yang Q, Zhang RW, Sui PC, He HT, Ding L. Dysregulation of non-coding RNAs in gastric cancer. World J Gastroenterol 2015;21:10956–81.10.3748/wjg.v21.i39.10956Search in Google Scholar

6. Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, et al. Circular RNA: a new star of non-coding RNAs. Cancer Lett 2015;365:141–8.10.1016/j.canlet.2015.06.003Search in Google Scholar

7. Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 1983;33:967–78.10.1016/0092-8674(83)90040-5Search in Google Scholar

8. Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 1983;97:329–39.10.1083/jcb.97.2.329Search in Google Scholar PubMed PubMed Central

9. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002;2:569–79.10.1038/nri855Search in Google Scholar PubMed

10. Keller S, Ridinger J, Rupp AK, Janssen JW, Altevogt P. Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med 2011;9:86.10.1186/1479-5876-9-86Search in Google Scholar PubMed PubMed Central

11. Zhou W, Fong MY, Min Y, Somlo G, Liu L, Palomares MR, et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014;25:501–15.10.1016/j.ccr.2014.03.007Search in Google Scholar PubMed PubMed Central

12. Wei Y, Lai X, Yu S, Chen S, Ma Y, Zhang Y, et al. Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat 2014;147:423–31.10.1007/s10549-014-3037-0Search in Google Scholar PubMed

13. Yu S, Liu C, Su K, Wang J, Liu Y, Zhang L, et al. Tumor exosomes inhibit differentiation of bone marrow dendritic cells. J Immunol 2007;178:6867–75.10.4049/jimmunol.178.11.6867Search in Google Scholar PubMed

14. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 2012;151:1542–56.10.1016/j.cell.2012.11.024Search in Google Scholar PubMed

15. Menck K, Klemm F, Gross JC, Pukrop T, Wenzel D, Binder C. Induction and transport of Wnt5a during macrophage-induced malignant invasion is mediated by two types of extracellular vesicles. Oncotarget 2013;4:2057–66.10.18632/oncotarget.1336Search in Google Scholar PubMed PubMed Central

16. Channavajjhala SK, Rossato M, Morandini F, Castagna A, Pizzolo F, Bazzoni F, et al. Optimizing the purification and analysis of miRNAs from urinary exosomes. Clin Chem Lab Med 2014;52:345–54.10.1515/cclm-2013-0562Search in Google Scholar PubMed

17. Conte D, Verri C, Borzi C, Suatoni P, Pastorino U, Sozzi G, et al. Novel method to detect microRNAs using chip-based QuantStudio 3D digital PCR. BMC Genomics 2015;16:849.10.1186/s12864-015-2097-9Search in Google Scholar PubMed PubMed Central

18. Jeong S, Park J, Pathania D, Castro CM, Weissleder R, Lee H. Integrated magneto-electrochemical sensor for exosome analysis. ACS Nano 2016;10:1802–9.10.1021/acsnano.5b07584Search in Google Scholar PubMed PubMed Central

19. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015;523:177–82.10.1038/nature14581Search in Google Scholar PubMed PubMed Central

20. Zlotogorski-Hurvitz A, Dayan D, Chaushu G, Salo T, Vered M. Morphological and molecular features of oral fluid-derived exosomes: oral cancer patients versus healthy individuals. J Cancer Res Clin Oncol 2016;142:101–10.10.1007/s00432-015-2005-3Search in Google Scholar PubMed

21. Silva J, Garcia V, Rodriguez M, Compte M, Cisneros E, Veguillas P, et al. Analysis of exosome release and its prognostic value in human colorectal cancer. Genes Chromosomes Cancer 2012; 51:409–18.10.1002/gcc.21926Search in Google Scholar PubMed

22. Manterola L, Guruceaga E, Gallego PJ, Gonzalez-Huarriz M, Jauregui P, Tejada S, et al. A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool. Neuro Oncol 2014;16:520–7.10.1093/neuonc/not218Search in Google Scholar PubMed PubMed Central

23. Shi R, Wang PY, Li XY, Chen JX, Li Y, Zhang XZ, et al. Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients. Oncotarget 2015;6:26971–81.10.18632/oncotarget.4699Search in Google Scholar PubMed PubMed Central

24. Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, et al. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol 2013;8:1156–62.10.1097/JTO.0b013e318299ac32Search in Google Scholar PubMed PubMed Central

25. Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer 2009;10:42–6.10.3816/CLC.2009.n.006Search in Google Scholar PubMed

26. Li Q, Shao Y, Zhang X, Zheng T, Miao M, Qin L, et al. Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumour Biol 2015;36:2007–12.10.1007/s13277-014-2807-ySearch in Google Scholar PubMed

27. Tokuhisa M, Ichikawa Y, Kosaka N, Ochiya T, Yashiro M, Hirakawa K, et al. Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer. PLoS One 2015;10:e130472.10.1371/journal.pone.0130472Search in Google Scholar PubMed PubMed Central

28. Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 2014;9:e92921.10.1371/journal.pone.0092921Search in Google Scholar PubMed PubMed Central

29. Matsumura T, Sugimachi K, Iinuma H, Takahashi Y, Kurashige J, Sawada G, et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer 2015;113:275–81.10.1038/bjc.2015.201Search in Google Scholar PubMed PubMed Central

30. Que R, Ding G, Chen J, Cao L. Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma. World J Surg Oncol 2013;11:219.10.1186/1477-7819-11-219Search in Google Scholar PubMed PubMed Central

31. Madhavan B, Yue S, Galli U, Rana S, Gross W, Muller M, et al. Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity. Int J Cancer 2015;136:2616–27.10.1002/ijc.29324Search in Google Scholar PubMed

32. Sohn W, Kim J, Kang SH, Yang SR, Cho JY, Cho HC, et al. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med 2015;47:e184.10.1038/emm.2015.68Search in Google Scholar PubMed PubMed Central

33. Sugimachi K, Matsumura T, Hirata H, Uchi R, Ueda M, Ueo 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;112:532–8.10.1038/bjc.2014.621Search in Google Scholar PubMed PubMed Central

34. Chiam K, Wang T, Watson DI, Mayne GC, Irvine TS, Bright T, et al. Circulating serum exosomal miRNAs as potential biomarkers for esophageal adenocarcinoma. J Gastrointest Surg 2015;19:1208–15.10.1007/s11605-015-2829-9Search in Google Scholar PubMed

35. Warnecke-Eberz U, Chon SH, Holscher AH, Drebber U, Bollschweiler E. Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor. Tumour Biol 2015;36:4643–53.10.1007/s13277-015-3112-0Search in Google Scholar PubMed

36. Armstrong DA, Green BB, Seigne JD, Schned AR, Marsit CJ. MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer. Mol Cancer 2015;14:194.10.1186/s12943-015-0466-2Search in Google Scholar PubMed PubMed Central

37. Huang X, Yuan T, Liang M, Du M, Xia S, Dittmar R, et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol 2015;67:33–41.10.1016/j.eururo.2014.07.035Search in Google Scholar PubMed PubMed Central

38. Samsonov R, Shtam T, Burdakov V, Glotov A, Tsyrlina E, Berstein L, et al. Lectin-induced agglutination method of urinary exosomes isolation followed by mi-RNA analysis: Application for prostate cancer diagnostic. Prostate 2016;76:68–79.10.1002/pros.23101Search in Google Scholar PubMed

39. Isin M, Uysaler E, Ozgur E, Koseoglu H, Sanli O, Yucel OB, et al. Exosomal lncRNA-p21 levels may help to distinguish prostate cancer from benign disease. Front Genet 2015;6:168.10.3389/fgene.2015.00168Search in Google Scholar

40. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 2008;110:13–21.10.1016/j.ygyno.2008.04.033Search in Google Scholar PubMed

41. Zhou J, Gong G, Tan H, Dai F, Zhu X, Chen Y, et al. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma. Oncol Rep 2015;33:2915–23.10.3892/or.2015.3937Search in Google Scholar PubMed

42. Liu J, Sun H, Wang X, Yu Q, Li S, Yu X, et al. Increased exosomal microRNA-21 and microRNA-146a levels in the cervicovaginal lavage specimens of patients with cervical cancer. Int J Mol Sci 2014;15:758–73.10.3390/ijms15010758Search in Google Scholar PubMed PubMed Central

43. Eichelser C, Stuckrath I, Muller V, Milde-Langosch K, Wikman H, Pantel K, et al. Increased serum levels of circulating exosomal microRNA-373 in receptor-negative breast cancer patients. Oncotarget 2014;5:9650–63.10.18632/oncotarget.2520Search in Google Scholar PubMed PubMed Central

44. Alegre E, Sanmamed MF, Rodriguez C, Carranza O, Martin-Algarra S, Gonzalez A. Study of circulating microRNA-125b levels in serum exosomes in advanced melanoma. Arch Pathol Lab Med 2014;138:828–32.10.5858/arpa.2013-0134-OASearch in Google Scholar PubMed

45. Ragusa M, Barbagallo C, Statello L, Caltabiano R, Russo A, Puzzo L, et al. miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: Pathological and diagnostic implications. Cancer Biol Ther 2015;16:1387–96.10.1080/15384047.2015.1046021Search in Google Scholar PubMed PubMed Central

46. Hornick NI, Huan J, Doron B, Goloviznina NA, Lapidus J, Chang BH, et al. Serum Exosome microRNA as a minimally-invasive early biomarker of AML. Sci Rep 2015;5:11295.10.1038/srep11295Search in Google Scholar PubMed PubMed Central

Received: 2016-1-11
Accepted: 2016-3-18
Published Online: 2016-5-11
Published in Print: 2016-12-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Biomarkers, inflammation and cancer: where to go?
  4. Review
  5. Analysis, detection and quantitation of mixed cryoglobulins in HCV infection: brief review and case examples
  6. Mini Reviews
  7. Calcitonin measurement and immunoassay interference: a case report and literature review
  8. Exosomal non-coding RNAs: a promising cancer biomarker
  9. Opinion Paper
  10. Towards a new paradigm in laboratory medicine: the five rights
  11. EFLM Recommendation
  12. Recommendation for the review of biological reference intervals in medical laboratories
  13. IFCC Position Paper
  14. Assuring the quality of interpretative comments in clinical chemistry
  15. General Clinical Chemistry and Laboratory Medicine
  16. The effect of centrifugation speed and time on pre-analytical platelet activation
  17. An assessment of clinical laboratory performance for the determination of manganese in blood and urine
  18. Evaluation of antiphospholipid antibody assays using latent class analysis to address the lack of a reference standard
  19. Evaluation of the hypochromic erythrocyte and reticulocyte hemoglobin content provided by the Sysmex XE-5000 analyzer in diagnosis of iron deficiency erythropoiesis
  20. Cancer Diagnosis
  21. Identifying risk in the use of tumor markers to improve patient safety
  22. Association between Echinococcus granulosus infection and cancer risk – a pilot study in Cyprus
  23. Dynamic change of the systemic immune inflammation index predicts the prognosis of patients with hepatocellular carcinoma after curative resection
  24. Aberrant methylation of tumour suppressor genes WT1, GATA5 and PAX5 in hepatocellular carcinoma
  25. Cardiovascular Diseases
  26. High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment
  27. Hemolysis and Coagulation
  28. Hemolysis rates in blood samples: differences between blood collected by clinicians and nurses and the effect of phlebotomy training
  29. Letters to the Editor
  30. Harmonisation of the laboratory testing process: need for a coordinated approach
  31. Pseudohyperkalemia due to severe leukocytosis: case presentation
  32. When obtaining a blood sample from the right arm was not the right thing to do: a case of elevated parathyroid hormone levels 27 years after thyroidectomy
  33. Raising awareness of assay compatibility with heparinized plasma
  34. Improved protocol for extraction of genomic DNA from formalin-fixed paraffin-embedded tissue samples without the use of xylene
  35. Effect of refrigeration, centrifugation, acidification, heat treatment and storage on urine calcium, magnesium and phosphate
  36. Letter in response to: Identifying risk in the use of tumor markers to improve patient safety
  37. Letter to the Editor in reply to Dayyani and Morgenstern’s comment on the article “Identifying risk in the use of tumor markers to improve patient safety”
  38. Level of red cell distribution width is affected by various factors
  39. Red blood cell distribution: an index without additional cost in estimating the prognosis of acute pancreatitis
  40. Testing of total 25(OH)vitamin D: agreement and discrepant cases between Cobas® 8000 and Liaison® XL methods
  41. Expression profiling and ontology analysis of circulating long non-coding RNAs in septic acute kidney injury patients
https://doi.org/10.1515/cclm-2016-0029
Keywords for this article
biomarker; cancer; exosomes; non-coding RNAs

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Biomarkers, inflammation and cancer: where to go?
  4. Review
  5. Analysis, detection and quantitation of mixed cryoglobulins in HCV infection: brief review and case examples
  6. Mini Reviews
  7. Calcitonin measurement and immunoassay interference: a case report and literature review
  8. Exosomal non-coding RNAs: a promising cancer biomarker
  9. Opinion Paper
  10. Towards a new paradigm in laboratory medicine: the five rights
  11. EFLM Recommendation
  12. Recommendation for the review of biological reference intervals in medical laboratories
  13. IFCC Position Paper
  14. Assuring the quality of interpretative comments in clinical chemistry
  15. General Clinical Chemistry and Laboratory Medicine
  16. The effect of centrifugation speed and time on pre-analytical platelet activation
  17. An assessment of clinical laboratory performance for the determination of manganese in blood and urine
  18. Evaluation of antiphospholipid antibody assays using latent class analysis to address the lack of a reference standard
  19. Evaluation of the hypochromic erythrocyte and reticulocyte hemoglobin content provided by the Sysmex XE-5000 analyzer in diagnosis of iron deficiency erythropoiesis
  20. Cancer Diagnosis
  21. Identifying risk in the use of tumor markers to improve patient safety
  22. Association between Echinococcus granulosus infection and cancer risk – a pilot study in Cyprus
  23. Dynamic change of the systemic immune inflammation index predicts the prognosis of patients with hepatocellular carcinoma after curative resection
  24. Aberrant methylation of tumour suppressor genes WT1, GATA5 and PAX5 in hepatocellular carcinoma
  25. Cardiovascular Diseases
  26. High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment
  27. Hemolysis and Coagulation
  28. Hemolysis rates in blood samples: differences between blood collected by clinicians and nurses and the effect of phlebotomy training
  29. Letters to the Editor
  30. Harmonisation of the laboratory testing process: need for a coordinated approach
  31. Pseudohyperkalemia due to severe leukocytosis: case presentation
  32. When obtaining a blood sample from the right arm was not the right thing to do: a case of elevated parathyroid hormone levels 27 years after thyroidectomy
  33. Raising awareness of assay compatibility with heparinized plasma
  34. Improved protocol for extraction of genomic DNA from formalin-fixed paraffin-embedded tissue samples without the use of xylene
  35. Effect of refrigeration, centrifugation, acidification, heat treatment and storage on urine calcium, magnesium and phosphate
  36. Letter in response to: Identifying risk in the use of tumor markers to improve patient safety
  37. Letter to the Editor in reply to Dayyani and Morgenstern’s comment on the article “Identifying risk in the use of tumor markers to improve patient safety”
  38. Level of red cell distribution width is affected by various factors
  39. Red blood cell distribution: an index without additional cost in estimating the prognosis of acute pancreatitis
  40. Testing of total 25(OH)vitamin D: agreement and discrepant cases between Cobas® 8000 and Liaison® XL methods
  41. Expression profiling and ontology analysis of circulating long non-coding RNAs in septic acute kidney injury patients
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 7.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2016-0029/html
Scroll to top button