Hye Ju Yu (Dept of Chemistry, Yonsei University)

Hye Ju Yu (Dept of Chemistry, Yonsei University)

Hye Ju Yu (Dept of Chemistry, Yonsei University)

Myeong Hee Moon (Dept of Chemistry, Yonsei University)

Exosomes, small extracellular vesicles ranging from 30 to 150 nm in diameter, are released from cells and contain lipids, proteins, DNA, and RNA. These vesicles reflect the biological state of their originating cells, thus providing insights into the health status of tissues and organs. Currently, research on exosomal lipidomics as biomarker development is actively ongoing. Extrahepatic cholangiocarcinoma (ECC), characterized by a 5-year survival rate of approximately 10% and lacking effective molecular targeted therapies, underscores the need for investigating biomarker candidates. In this study, exosomal lipids from serum samples of ECC patients were analyzed using the two analytical platforms, nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry (nUHPLC-ESI-MS/MS) and online miniaturized asymmetrical flow field-flow fractionation coupled with electrospray ionization-tandem mass spectrometry (mFlFFF-ESI-MS/MS) for the development of top-down lipidomic analysis of exosomes. By nUHPLC-ESI-MS/MS, 61 lipids showing significant differences (>1.5-fold) were targeted, and by mFlFFF-ESI-MS/MS, 17 lipids showing significant differences (>1.5-fold; p<0.05 and AUC>0.800) were selected as biomarker candidates from the target lipids. This study demonstrated the potential of mFlFFF-ESI-MS/MS for high-speed (<15 min) quantification of exosomal lipids and identified potential biomarkers for ECC.

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