Abstract
Peripheral nerve sheath tumors (PNSTs) include schwannomas, neurofibromas (NFs), and plexiform neurofibromas (PNFs), among others. While they are benign tumors, according to their biological behavior, some have the potential for malignant degeneration, mainly PNFs. The specific factors contributing to the more aggressive behavior of some PNSTs compared to others are not precisely known. Considering that lipid homeostasis plays a crucial role in fibrotic/inflammatory processes and in several cancers, we hypothesized that the lipid asset was also unbalanced in this group of nerve tumors. Through untargeted lipidomics, NFs presented a significant increase in ceramide, phosphatidylcholine, and Vitamin A ester. PNFs displayed a marked decrease in 34 out of 50 lipid class analyzed. An increased level of ether- and oxidized-triacylglycerols was observed; phosphatidylcholines were reduced. After sphingolipidomic analysis, we observed six sphingolipid classes. Ceramide and dihydroceramides were statistically increased in NFs. All the glycosylated species appeared reduced in NFs, but increased in PNFs. Our findings suggested that different subtypes of PNSTs presented a specific modulation in the lipidic profile. The untargeted and targeted lipidomic approaches, which were not applied until now, contribute to better clarifying bioactive lipid roles in PNS natural history to highlight disease molecular features and pathogenesis.
Highlights
To understand the cross-talk between the lipid profile and the tumor characteristics, we evaluated, for the first time, the lipidomic profile of different Peripheral nerve sheath tumors (PNSTs) obtained from neurosurgical procedures in patients with sporadic tumors or associated with neurocutaneous diseases
Schwannomas showed a marked increase of coenzyme Q10 (CoQ, p < 0.05), ether lysoschwannomas showed a marked increase of coenzyme Q10 (CoQ, p < 0.05), ether lysophosphospholipids, hexosylceramides (HexCer), whereas ether phospholipids, ether triglycerpholipids, hexosylceramides (HexCer), whereas ether phospholipids, ether triglycerides, ides, and sphingomyelins were reduced (Figure 2)
Discussion this approach, we obtained a lipid profile assessment among different subtypes of PNSTs derived from neurosurgical procedures in patients with sporadic or neurocutaneous-related tumors to investigate the impact of lipid alterations on tumors features
Summary
Their capsule is more adherent to the central mass of the tumor than schwannomas They are constituted by Schwann cells and a non-neoplastic fibrous component that includes fibroblasts. PNFs present irregularly thickened, distorted, tortuous structures and are composed of neoplastic Schwann cells, fibroblasts, mast cells, macrophages, endothelial cells, nerve cells, and other cell types with abundant collagen deposition. They have the highest growth potential in childhood and adolescence, while the growth tends to slow down in adulthood [5–7]. By a targeted sphingolipidomic approach, the profile of this class of bioactive lipids, since sphingolipids are known to take part in immune response and can initiate or sustain inflammation and cellular apoptosis in inherited, fibrotic, and progressive. PNSTs, tumors lack studies addressing a pathogenic role for the lipid asset
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