Abstract 697P
Background
Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer and its main etiological factors are smoking, alcohol consumption and HPV infection. OSCC metabolic profile is heterogeneous and related to mutations in several tumor suppressor genes and oncogenes. Patterns have become apparent, such as increased choline metabolism, which indicates active proliferation. Phosphatidylcholine (PC) is a key component of membranes and source of signaling molecules. The project aimed to analyze the glycerophospholipid profile in OSCC patients compared with control samples using mass spectrometry and gene expression techniques to analyze blood, tissue and clinical-pathological characteristics.
Methods
The blood analysis was performed by LC-MS/MS using the AbsoluteIDQ p180 Kit in 61 untreated OSCC and 60 controls. MALDI-MSI was performed using a RapifleX Tissuetyper (Bruker Daltonik) in 54 non microdissected samples of OSCC from untreated patients. The MS data was confirmed by DDA using an Orbitrap Elite (Thermo Fisher Scientific) coupled to a MALDI source. Gene expression analysis was performed in a 7500 Fast Real-Time PCR (Applied Biosystems).
Results
We found altered gene expression related with the conversion of phosphocholine to PC between cancer and normal tissue. We found high levels of unsaturated PC and sphingomyelins in patients with OSCC compared to controls matched by sex and age and also related with cancer progression. This result may indicate an altered lipid synthesis and secretion and may represent de novo lipogenesis, a requirement of cancer cell proliferation. The comparison of cases with lymph node clinically positive for metastases (cN+) and controls had an AUC of 0.912 (95% CI: 0.832-0.983), which indicates that certain metabolites may be important for clinical decisions regarding management of patients. The MSI approach showed alterations in lipid profiles between tumor and health tissue.
Conclusions
The OSCC patients exhibited a distinct plasma metabolic profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is more evident in advanced stages of the disease and may contribute to proliferation and inflammation. Such a signature, if used in monitoring tests, may contribute to prognosis and treatment of OSCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo; Maastricht MultiModal Molecular Imaging Institute – M4i.
Funding
FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo; Maastricht MultiModal Molecular Imaging Institute – M4i.
Disclosure
All authors have declared no conflicts of interest.