Abstract
Oral squamous cell carcinoma (OSCC) accounting for about 90% of malignant oral lesions is the 6th most common malignancy worldwide. Diagnostic delay may contribute to dismal survival rate therefore, there is a need for developing specific and sensitive biomarkers to improve early detection. Hungarian population occupies the top places of statistics regarding OSCC incidence and mortality figures therefore, we aimed at finding potential salivary protein biomarkers suitable for the Hungarian population. In this study we investigated 14 proteins which were previously reported as significantly elevated in saliva of patients with OSCC. In case of IL-1α, IL-1β, IL-6, IL-8, TNF-α and VEGF a Luminex-based multiplex kit was utilized and the salivary concentrations were determined. In case of catalase, profilin-1, S100A9, CD59, galectin-3-bindig protein, CD44, thioredoxin and keratin-19, SRM-based targeted proteomic method was developed and the relative amount of the proteins was determined in the saliva of patients with OSCC and controls. After several rounds of optimization and using stable isotope-containing peptides, we developed an SRM-based method for rapid salivary protein detection. The validation of the selected potential biomarkers by ELISA revealed salivary protein S100A9 and IL-6 as useful protein biomarkers for OSCC detection improving the diagnostic accuracy for OSCC in the Hungarian population.A noninvasive diagnostic method to detect biomarkers useful for the early diagnosis of OSCC was developed. This can be an attractive strategy in screening saliva samples collected in a nation-wide multi-centric study in order to decrease morbidity, mortality, to enhance survival rate and to improve quality of life. The heterogeneity of protein biomarkers found in different ethnic groups presented in the literature highlights the importance of identification of population-tailored protein biomarkers.
Highlights
With 350,000–400,000 new cases annually, oral cavity squamous cell carcinomas (OSCC) represent a major health-care problem worldwide
Application of Selected reaction monitoring (SRM)-based targeted proteomics platform was already used for salivary protein biomarker detection [16] and our aim was to test if some of the potential salivary protein biomarkers already described in scientific literature can be used in the Hungarian population for OSCC detections. In this prospective study we report on the detection of salivary biomarkers in accordance to the Clinical Proteomic Technologies for Cancer (CPTC) initiative guidelines established by the National Cancer Institute [17]
Detection of salivary biomarkers which can help in the early diagnosis of OSCC is of high importance in improving survival rates of patients with OSCC
Summary
With 350,000–400,000 new cases annually, oral cavity squamous cell carcinomas (OSCC) represent a major health-care problem worldwide. The increasing incidence of OSCC among women and young and middle-aged males is challenging [1,2,3,4]. Hungarian women and men occupy the top places of statistics regarding global OSCC incidence and mortality figures with an embarrassing fourfold elevation of overall OSCC mortality rate in Hungary by the new millennium since the 1970-ies [6]. I.e. expert clinical examination and histological evaluation of suspicious areas fail to detect the majority of patients with early stage OSCC so improvement of the diagnostic methods is required [5,8]. Salivary protein biomarkers may represent a promising tool for improving clinical outcome of patients with OSCC
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