Serum metabolomics reveals distinctive signature of cancer staging in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer. It is of great significance to search for biomarkers associated with OSCC progression through minimally invasive methods. Conductive polymer spray ionization mass spectrometry (CPSI-MS) was used to perform a rapid metabolic analysis of trace volume serum from OSCC and healthy controls. Key metabolites were identified by receiver operating characteristic (ROC) curves and further validated by desorption electrospray ionization mass spectrometry (DESI-MSI) and ultra–high performance liquid chromatography-tandem mass spectrometer (UHPLC-MS/MS). The study identified 125 metabolites that significantly differentiated early-stage OSCC from healthy controls. 47 metabolites showed an upward or downward trend in the OSCC staging (I-IV). Through ROC curve analysis and trend assessment of metabolite levels, 10 key metabolites associated with OSCC staging were pinpointed. KEGG pathway enrichment analysis showed that glycerophospholipid metabolism is closely related to OSCC staging. Representative serum metabolites were validated by DESI-MS and UHPLC-MS/MS at tissue level. Kaplan-Meier (KM) survival analysis showed that PC (40:6) was an independent prognostic factor for OSCC. We identified 10 metabolites associated with OSCC staging, and found that glycerophospholipid metabolism may promote the progression of OSCC. Moreover, the key metabolite PC(40:6) is closely related to the prognosis of OSCC.