Profile of sphingolipids in head and neck cancer

Author(s)

Raquel Roman Faedo

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2021-08-09

Examining board members

Andréia Machado Leopoldino; Luiz Carlos Conti de Freitas; Flávia Cristina Rodrigues Lisoni

• Advisor: Andréia Machado Leopoldino

Abstract

Sphingolipids are a class of essential lipids in eukaryotes not only by composing the plasma membrane but because they are bioactive molecules. Because of the large number of pathways that these molecules regulate, the imbalance in their metabolism triggers a series of pathologies, such as cancer. In head and neck cell carcinoma (HNSCC) patients, the reduction in ceramide level was associated with tumor progression and worse prognosis, but other sphingolipids were not evaluated. In the present study, we propose to determine the profile of sphingolipids in samples from patients with head and neck squamous cell carcinoma and to search association with clinical and pathological parameters. Moreover, we study the relationship between sphingolipids and SET overexpression in oral keratinocyte cell lineage (NOK-SI), due to this protein is accumulated in HNSCC. Samples of plasma (n=56), tumor and surgical margin tissues (n=84) from HNSCC patients, plasma from control group (n= 58) and NOK-SI/SET cells were used for lipids extraction. The sphingolipids were analyzed by liquid chromatography-mass spectrometry. As expected, we found that stage, tumor size, lymph node metastasis, perineural invasion, and angiolymphatic invasion affect HNSCC patient survival. Therefore, our results showed difference between sphingolipids plasma profile of HNSCC patients compared to controls. Also, alterations in some sphingolipid molecules in plasma may be indicators of worse prognosis in HNSCC. In the tumor tissue, twelve sphingolipids were associated with clinical and pathological parameters, being that the alterations of specific sphingolipids were related to more aggressive parameters. Furthermore, we evaluated the potential of these molecules as candidates for diagnostic markers in plasma, and six of them showed promise, as well as the combinations of some of them have high sensitivity and specificity. Finally, the accumulation of SET protein in NOK-SI cells induced alterations in sphingolipids profile, suggesting a SET role in metabolism of sphingolipids. In conclusion, we propose the altered sphingolipids as potential candidates for diagnostic and prognostic markers in HNSCC. Further studies will be needed to understand how the sphingolipids are related to head and neck cancer progression. (AU)

• FAPESP's process: 18/03278-3 - Profile of sphingolipids in head and neck cancer
• Grantee: Raquel Roman Faedo
• Support Opportunities: Scholarships in Brazil - Master