Source of Liquid Biopsy Biomarker: Exosome vs Whole Plasma, Fasting vs Non-fasting

Abstract Background The liquid biopsy using plasma samples is being studied to find biomarkers for clinical applications. Exosomes encompass nucleic acids and metabolites that have been highlighted as a potential biomarker source. To test the efficacy of exosomes over plasma, we compared the profiles of small non-coding RNAs (ncRNAs) and metabolites extracted from exosomes (which were purified from plasma) to the profiles extracted directly from whole plasma. The fasting and non-fasting status of the samples were also compared. Results We found that ncRNA profiles were not affected by fasting for both exosomal and plasma samples. Our results showed that ncRNAs extracted from exosomes were found to have the more consistent profiles between fasting and non-fasting samples. The whole plasma RNA profiles contained high concentrations of cell-derived miRNAs that were likely based on hemolysis. We also found that some metabolites in whole plasma showed significant changes in concentration due to fasting status, whereas others did not. Conclusions Here, we propose that 1) fasting isn’t necessary for liquid biopsy study for both circulating ncRNA and metabolomic profiling as long as metabolites which aren’t affected by fasting status are chosen. 2) Exosomal RNAs must be used to obtain consistent results without batch effects in plasma samples due to different levels of hemolysis.