Secreted Down Regulated Protein Markers in Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is the key reason for illness and death by oral cancer. The discovery of candidate markers to differentiate normal from malignant cells can result in an accurate and early clinical diagnosis of OSCC. We aimed to identify candidate biomarkers for OSCC diagnosis and to enhance understanding of their role in disease progression and pathogenesis. Of particular interest are proteins that are secreted in saliva to allow non-invasive detection. We employed a high throughput protein profiling approach involving single shot peptide fractionation coupled to mass spectrometry analysis of the fourteen paired human malignant OSCC and normal adjacent mucous samples to identify protein markers. We found a total of 5,123 protein fractions in the proteome dataset of OSCC and normal samples, including 94 proteins with strong differential expression (p-value <0.01 and the fold change <-2). Functional data analysis revealed that these 94 down-regulated proteins were significantly associated with multiple biological processes, like myogenesis, fatty acid metabolism, and KRAS Signaling. To further highlight candidate markers for non-invasive OSCC detection, we combined our data with public salivary datasets, identifying 3 candidate markers for further study. Our investigation identified proteins and TF involved in key pathways regulating them is likely to provide insight into the mechanism of OSCC progression which may lead to developing novel OSCC diagnostics and therapeutics strategies.