Exploring Optimal Biomarker Sources: A Comparative Analysis of Exosomes and Whole Plasma in Fasting and Non-Fasting Conditions for Liquid Biopsy Applications

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jan 11

PMID 38203541

Authors

Masaki Nasu

Vedbar S Khadka

Mayumi Jijiwa

Ken Kobayashi

Youping Deng

Affiliations

Soon will be listed here.

Abstract

The study of liquid biopsy with plasma samples is being conducted to identify biomarkers for clinical use. Exosomes, containing nucleic acids and metabolites, have emerged as possible sources for biomarkers. To evaluate the effectiveness of exosomes over plasma, we analyzed the small non-coding RNAs (sncRNAs) and metabolites extracted from exosomes in comparison to those directly extracted from whole plasma under both fasting and non-fasting conditions. We found that sncRNA profiles were not affected by fasting in either exosome or plasma samples. Our results showed that exosomal sncRNAs were found to have more consistent profiles. The plasma miRNA profiles contained high concentrations of cell-derived miRNAs that were likely due to hemolysis. We determined that certain metabolites in whole plasma exhibited noteworthy concentration shifts in relation to fasting status, while others did not. Here, we propose that (1) fasting is not required for a liquid biopsy study that involves both sncRNA and metabolomic profiling, as long as metabolites that are not influenced by fasting status are selected, and (2) the utilization of exosomal RNAs promotes robust and consistent findings in plasma samples, mitigating the impact of batch effects derived from hemolysis. These findings advance the optimization of liquid biopsy methodologies for clinical applications.

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References

Zhang L, Zhu B, Zeng Y, Shen H, Zhang J, Wang X . Clinical lipidomics in understanding of lung cancer: Opportunity and challenge. Cancer Lett. 2019; 470:75-83. DOI: 10.1016/j.canlet.2019.08.014. View

Yu H, Guan Z, Cuk K, Brenner H, Zhang Y . Circulating microRNA biomarkers for lung cancer detection in Western populations. Cancer Med. 2018; 7(10):4849-4862. PMC: 6198213. DOI: 10.1002/cam4.1782. View

Simundic A, Cornes M, Grankvist K, Lippi G, Nybo M . Standardization of collection requirements for fasting samples: for the Working Group on Preanalytical Phase (WG-PA) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). Clin Chim Acta. 2013; 432:33-7. DOI: 10.1016/j.cca.2013.11.008. View

Slomka A, Kornek M, Cho W . Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review. Cells. 2022; 11(18). PMC: 9496799. DOI: 10.3390/cells11182913. View

Sun L, Yu Y, Niu B, Wang D . Red Blood Cells as Potential Repositories of MicroRNAs in the Circulatory System. Front Genet. 2020; 11:442. PMC: 7286224. DOI: 10.3389/fgene.2020.00442. View

Wang K, Yuan Y, Cho J, McClarty S, Baxter D, Galas D . Comparing the MicroRNA spectrum between serum and plasma. PLoS One. 2012; 7(7):e41561. PMC: 3409228. DOI: 10.1371/journal.pone.0041561. View

Markert L, Holdmann J, Klinger C, Kaufmann M, Schork K, Turewicz M . Small RNAs as biomarkers to differentiate benign and malign prostate diseases: An alternative for transrectal punch biopsy of the prostate?. PLoS One. 2021; 16(3):e0247930. PMC: 7990312. DOI: 10.1371/journal.pone.0247930. View

Slonchak A, Clarke B, Mackenzie J, Amarilla A, Setoh Y, Khromykh A . West Nile virus infection and interferon alpha treatment alter the spectrum and the levels of coding and noncoding host RNAs secreted in extracellular vesicles. BMC Genomics. 2019; 20(1):474. PMC: 6558756. DOI: 10.1186/s12864-019-5835-6. View

Townsend M, Bao Y, Poole E, Bertrand K, Kraft P, Wolpin B . Impact of Pre-analytic Blood Sample Collection Factors on Metabolomics. Cancer Epidemiol Biomarkers Prev. 2016; 25(5):823-829. PMC: 4873428. DOI: 10.1158/1055-9965.EPI-15-1206. View

10.

Taylor C, Chacko S, Davey M, Lacroix J, MacPherson A, Finn N . Peptide-Affinity Precipitation of Extracellular Vesicles and Cell-Free DNA Improves Sequencing Performance for the Detection of Pathogenic Mutations in Lung Cancer Patient Plasma. Int J Mol Sci. 2020; 21(23). PMC: 7730179. DOI: 10.3390/ijms21239083. View

11.

Wakabayashi I, Sotoda Y, Eguchi R . Relationships among erythrocyte-derived microRNAs in serum of healthy donors. Clin Chim Acta. 2020; 507:7-10. DOI: 10.1016/j.cca.2020.03.034. View

12.

Singh P, Patel A, Kaffenes A, Hord C, Kesterson D, Prakash S . Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics. Micromachines (Basel). 2022; 13(1). PMC: 8778688. DOI: 10.3390/mi13010139. View

13.

Aqil F, Gupta R . Exosomes in Cancer Therapy. Cancers (Basel). 2022; 14(3). PMC: 8833672. DOI: 10.3390/cancers14030500. View

14.

Vasconcelos M, Caires H, Abols A, Xavier C, Line A . Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance. Drug Resist Updat. 2019; 47:100647. DOI: 10.1016/j.drup.2019.100647. View

15.

Lee J, Kim M, Seong M, Kim H, Lee Y, Kang H . Plasma vs. serum in circulating tumor DNA measurement: characterization by DNA fragment sizing and digital droplet polymerase chain reaction. Clin Chem Lab Med. 2019; 58(4):527-532. DOI: 10.1515/cclm-2019-0896. View

16.

Costa C, de Almeida I, Jakobs C, Poll-The B, Duran M . Dynamic changes of plasma acylcarnitine levels induced by fasting and sunflower oil challenge test in children. Pediatr Res. 1999; 46(4):440-4. DOI: 10.1203/00006450-199910000-00013. View

17.

Chen J, Li P, Zhang T, Xu Z, Huang X, Wang R . Review on Strategies and Technologies for Exosome Isolation and Purification. Front Bioeng Biotechnol. 2022; 9:811971. PMC: 8766409. DOI: 10.3389/fbioe.2021.811971. View

18.

Maues J, Moreira-Nunes C, Burbano R . MicroRNAs as a Potential Quality Measurement Tool of Platelet Concentrate Stored in Blood Banks-A Review. Cells. 2019; 8(10). PMC: 6829606. DOI: 10.3390/cells8101256. View

19.

Nordestgaard B, Langsted A, Mora S, Kolovou G, Baum H, Bruckert E . Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European.... Eur Heart J. 2016; 37(25):1944-58. PMC: 4929379. DOI: 10.1093/eurheartj/ehw152. View

20.

Challagundla K, Wise P, Neviani P, Chava H, Murtadha M, Xu T . Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy. J Natl Cancer Inst. 2015; 107(7). PMC: 4651042. DOI: 10.1093/jnci/djv135. View