Lipid Biomarkers in Liquid Biopsies: Novel Opportunities for Cancer Diagnosis

Abstract

Altered cellular metabolism is a well-established hallmark of cancer. Although most studies have focused on the metabolism of glucose and glutamine, the upregulation of lipid metabolism is also frequent in cells undergoing oncogenic transformation. In fact, cancer cells need to meet the enhanced demand of plasma membrane synthesis and energy production to support their proliferation. Moreover, lipids are precursors of signaling molecules, termed lipid mediators, which play a role in shaping the tumor microenvironment. Recent methodological advances in lipid analysis have prompted studies aimed at investigating the whole lipid content of a sample (lipidome) to unravel the complexity of lipid changes in cancer patient biofluids. This review focuses on the application of mass spectrometry-based lipidomics for the discovery of cancer biomarkers. Here, we have summarized the main lipid alteration in cancer patients' biofluids and uncovered their potential use for the early detection of the disease and treatment selection. We also discuss the advantages of using biofluid-derived extracellular vesicles as a platform for lipid biomarker discovery. These vesicles have a molecular signature that is a fingerprint of their originating cells. Hence, the analysis of their molecular cargo has emerged as a promising strategy for the identification of sensitive and specific biomarkers compared to the analysis of the unprocessed biofluid.

Keywords: biofluids; biomarkers; cancer; extracellular vesicles; lipid metabolism; lipidomics; liquid biopsy; mass spectrometry.

Figure 1

Schematic illustration of membrane lipids. In the upper box, example of glycerophospholipids: phosphatidylserine (PS) 18:0/20:5, phosphatidylinositol (PI) 16:0/16:1, alkenyl ether (plasmalogen) phosphatidylethanolamine (PE) p20:0/22:2, lysophosphatidylcholine (LPC) 18:3 and lysophosphatidic acid (LPA) 16:0. The glycerol moiety is marked in light blue, and the polar head is marked in yellow. In the lower box, examples of sphingolipids: ceramide (Cer) d18:1/20:0, sphingomyelin (SM) d18:2/16:0 and lactosylceramide (LacCer) d18:1/20:0. The pink box highlights the long-chain base (LCB), sphingosine, and the yellow one highlights the polar head. Structures have been made using the Structure Drawing Tools available at Lipid Maps [15].