Towards Lipidomics of Low-Abundant Species for Exploring Tumor Heterogeneity Guided by High-Resolution Mass Spectrometry Imaging

Abstract

Many studies have evidenced the main role of lipids in physiological and also pathological processes such as cancer, diabetes or neurodegenerative diseases. The identification and the in situ localization of specific low-abundant lipid species involved in cancer biology are still challenging for both fundamental studies and lipid marker discovery. In this paper, we report the identification and the localization of specific isobaric minor phospholipids in human breast cancer xenografts by FTICR MALDI imaging supported by histochemistry. These potential candidates can be further confirmed by liquid chromatography coupled with electrospray mass spectrometry (LC-ESI-MS) after extraction from the region of interest defined by MALDI imaging. Finally, this study highlights the importance of characterizing the heterogeneous distribution of low-abundant lipid species, relevant in complex histological samples for biological purposes.

Tissue and serum lipidome shows altered lipid composition with diagnostic potential in mycosis fungoides

“…There are nine categories of lipids including fatty acids, glycerolipids, sphingolipids, glycerophospholipids, sterol lipids, prenolipids, saccharolipids, polyketides and sterols. Lipids are involved in many physiological metabolic pathways such as cell fusion/division, apoptosis, shape, membrane vesicle trafficking and signal transduction [ 11 ]. Altered lipid content is associated with many human diseases including diabetes, neurodegenerative diseases, heart disease and cancer [ 11 ].…”

MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation

“…Mass spectrometry imaging (MSI) has been recognized as a powerful tool for the molecular profiling and imaging of a variety of tumors. This technique has been used for characterizing molecules such as proteins, peptides, lipids, and metabolites in tissue samples (17)(18)(19)(20)(21)(22)(23)(24). Desorption electrospray ionization (DESI) coupled with MSI has already been shown to distinguish cancerous from noncancerous tissue, and studies validating its implementation in an operating room for real-time and near-real-time diagnosis have been presented (25)(26)(27)(28).…”

MALDI mass spectrometric imaging meets “omics”: recent advances in the fruitful marriage

“…The metabolome consists of small molecular building blocks (e.g., amino acids, nucleotides), metabolic intermediates (e.g., fatty acids), and structural and signalling elements (e.g., lipids). 143,144 Compared to the list of proteomic MALDI MSI studies in cancer research, as presented two sections above, this list is nearly as long. 140 Since lipids, which are classified as a subset of metabolomics, are playing many important roles in cancer progressing, 141 their spatial localization has been investigated in colorectal, 80 clear cell renal cell, 110 , thyroid, gastric, lung, esophageal, breast, 85 head and neck cancer, 50, 142 as well as xenografts.…”