Lipidomics and Cancer Research

Lipids have a variety of important biological functions due to their high complexity and diversity. For example, phospholipid bilayers that make up cell membranes maintain cellular stability, provide a suitable hydrophobic environment for cell membrane proteins and their interactions, and participate in cell growth, proliferation, and apoptosis. In recent years, some studies have found that lipids can also be used as potential biomarkers for diseases such as malignant cancers.

Lipidomics and Liver Cancer

Studies have shown that lipids such as lysophosphatidylcholine (LPC), phosphatidylcholine (PC), sphingomyelin (SP), triglycerides (TG), and cholesterol may be detected with varying degrees of differential lipid metabolism in patients with hepatitis B, cirrhosis, and liver cancer.

Highly saturated PC is biosynthesized from diglycerides and choline mainly in the CDP-choline pathway. Its highly saturated fatty acid chains protect cancer cells from cell death due to oxidative stress. Therefore, highly saturated PC is upregulated with cancer development. lPC is a subunit of lysophospholipase D (Lyso PLD) and autotaxin (ATX). lysoPLD/ATX converts LPC to lysophosphatidic acid LPA. During cancer development, Lyso PLD and ATX are overexpressed, which may lead to LPC downregulation.

PC, LPC, and LPE analogs are not only used as biomarkers of potential hepatocellular carcinoma to measure the development of disease in patients, but are also expected to be prognostic outcome indicators to predict the time and probability of recurrence.

Lipidomics and Breast Cancer

Cyclic phosphodiesterase A2 (cPLA2) is highly expressed in breast cancer cells. It was shown that the ratio of four phosphatidylcholine (PC) and the corresponding LPC regulated by cPLA2 is consistent with the activation of cPLA2 and can be further used to measure the metastatic potential of breast cancer cells.

Phosphatidylinositol (PI) (16:0/16:1) and PI (18:0/20:4) showed significant differences in levels in benign and malignant breast tumors and can be used as biomarkers of potential malignant breast tumors to distinguish between benign and malignant breast tumors. PI is a precursor of PIP3, which is involved in the PI3K/AKT pathway as a signaling lipid. The PI3K/AKT pathway plays an important role in the metabolism, survival, growth, proliferation, polarity and apoptosis of cells, including breast cancer cells. Cancer development stimulates PI3K/AKT downstream signaling and tumor growth, promotes PI depletion, and leads to PI downregulation.

Lipidomics and Prostate Cancer

The most commonly used biomarker for prostate cancer is serum prostate-specific antigen, however, its low specificity limits its use in the early diagnosis and prediction of prostate cancer. Lipidomic studies on prostate cancer have shown that serum levels of phospholipids, especially lyso-LPC and phosphatidylethanolamine (PE), are significantly lower in patients with prostate cancer than in normal subjects. There was a significant increase in PC and PI levels. These differential expressions provide new directions for the prediction of prostate cancer, as well as for the study of lipid metabolism in prostate cancer.

Analytical methods for lipidomics

Shotgun is an innovative lipidomics detection technique developed by Han XL based on ESI ion source and tandem mass spectrometry. A triple quadrupole mass spectrometer is typically used, with Q1 and Q3 typically used for mass separation and Q2 as a collision cell for collision activation-induced dissociation (CAD) fragmentation. The functions of precursor ion scan, productIon scan, neutral loss scan (NL), selected ion scan and multiple reaction monitor (MRM) can be achieved by adjusting the functions of the three four-stage rods.

The shotgun method is particularly suitable for the profile analysis of two differences, such as the analysis of differences after cell intervention through extracellular ligands or gene knockout. However, the shotgun method is not an ideal analytical method for trace levels of lipids. Its most obvious limitation is that it cannot achieve accurate quantification for low-abundance lipid samples.

Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) are more sensitive and can effectively differentiate isomers. LC-MS technology is the most widely used technique for lipidomic studies of a wide range of biological samples such as blood, cellular and tissue samples. GC-MS is particularly suitable for the analysis of long-chain fatty acids that are difficult to ionize in the case of liquid association.

Creative Proteomics has an advanced chromatography-mass spectrometry platform to provide professional lipidomics services for cancer-related research.

Reference:

1. Butler, L., Perone, Y., et al. (2020). Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Advanced drug delivery reviews.