Exosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. Researchers from the Oslo University Hospital have investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers.
A high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls.
Control samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes and exosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed.
Lipid classes in urinary exosomes
(A) Concentration (mol%) of lipid classes in urinary exosomes. The concentration of CHOL was divided by 4 to improve the visualisation of the other species. The insert shows the low abundant lipid classes. (B) Pie diagram showing the percentage of CHOL, phospholipids and SM in urinary exosomes. PC-3 cells–derived exosomes are shown for comparison. (C) Pie diagram showing phospholipid classes in urinary exosomes. In panel C, 100% corresponds to the 21% phospholipids shown in panel B. In B and C, phospholipids include the sum of all phospholipid classes excluding SM. The results are based on the quantification of 107 lipid species and the figure shows the mean and the standard error based on the analysis of four healthy males.