Abstract
Oral squamous cell carcinoma (OSCC) is a major health problem globally. Unfortunately Hungary has one of the highest incidences of OSCC in the world, therefore there is a great need for developing sensitive and specific biomarkers. Saliva has become increasingly important as a biological fluid for the detection of diagnostic and prognostic biomarkers.
Aim: The aim of this study was to identify and validate biomarkers characteristic for OSCC diagnosis in the Hungarian population.
Methods: Ethical approval was obtained from the University of Debrecen Ethics Committee (No. 3385-2011) and the subjects gave informed permission. The study population was formed of 41 patients with OSCC. Twenty four age matched and 10 young healthy volunteers who had no Human Papilloma Virus infection, diabetes mellitus or any autoimmune diseases acted as controls. Fourteen proteins previously identified as potential biomarkers were selected and examined. A targeted proteomics method was developed for catalase, thioredoxin, S100A9, galectin-3 binding protein, cytokeratin 21, profiling, CD44 and CD59. Their level was examined in saliva samples of OSCC patients, age matched controls and young controls. The level of IL-6, IL-8, IL-1b, IL-1a, TNFa and VEGF was examined in saliva samples using a custom 6plex Milliplex kit. The statistical analysis of mass spectrometry data was performed using MStat software. For cytokine measurement, the U-test was used.
Results: The levels of protein S100A9, thioredoxin, IL-6 and TNFa were significantly altered in OSCC patients compared to controls (p<0.05). A ROC analysis indicated that the combination of S100A9 and thioredoxin (AUC=0.8) and IL-6 (AUC=0.9) may act as potential OSCC biomarkers applicable for the Hungarian population. For validation, the levels of these potential biomarkers were analyzed in 200 saliva samples collected in a multi centric study from the patients of the four University Medical Centers (Debrecen, Budapest, Pecs and Szeged) in Hungary using ELISA.
Conclusions: The results of this study indicate that the combination of protein S100A9, thioredoxin and IL-6 seem to be useful biomarkers for OSCC detection in the Hungarian population.
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