Abstract
One of the most common cancers worldwide is oral squamous cell carcinoma (OSCC), which is associated with a significant death rate and has been linked to several risk factors. Notably, failure to detect these neoplasms at an early stage represents a fundamental barrier to improving the survival and quality of life of OSCC patients. In the present study, serum samples from OSCC patients (n = 25) and healthy controls (n = 25) were subjected to two-dimensional gel electrophoresis (2-DE) and silver staining in order to identify biomarkers that might allow early diagnosis. In this regard, 2-DE spots corresponding to various up- and down-regulated proteins were sequenced via high-resolution MALDI-TOF mass spectrometry and analyzed using the MASCOT database. We identified the following differentially expressed host-specific proteins within sera from OSCC patients: leucine-rich α2-glycoprotein (LRG), alpha-1-B-glycoprotein (ABG), clusterin (CLU), PRO2044, haptoglobin (HAP), complement C3c (C3), proapolipoprotein A1 (proapo-A1), and retinol-binding protein 4 precursor (RBP4). Moreover, five non-host factors were detected, including bacterial antigens from Acinetobacter lwoffii, Burkholderia multivorans, Myxococcus xanthus, Laribacter hongkongensis, and Streptococcus salivarius. Subsequently, we analyzed the immunogenicity of these proteins using pooled sera from OSCC patients. In this regard, five of these candidate biomarkers were found to be immunoreactive: CLU, HAP, C3, proapo-A1 and RBP4. Taken together, our immunoproteomics approach has identified various serum biomarkers that could facilitate the development of early diagnostic tools for OSCC.
Highlights
Oral cancer represents the sixth most prevalent cancer in the world
Protein spots in the 2-DE gels from oral squamous cell carcinoma (OSCC) patients (n = 25) and normal controls (n = 25) were analyzed using PDQuest 2-D gel analysis software
Based on the analysis in category 3 (Fig. 2C), our results show that the healthy control serums have the autoantibodies against OSCC serum antigens, CLU, C3, proapo-A1, and retinol-binding protein 4 precursor (RBP4), which are the host-specific proteins that showed the most immunoreactivity in the immunoblot
Summary
Oral cancer represents the sixth most prevalent cancer in the world. Among the different types of oral cancer, oral squamous cell carcinoma (OSCC) arising from the oral mucosa accounts for more than 90% of these malignancies. Despite recent advances in the diagnosis and treatment of oral cancer (e.g., chemotherapy, radiotherapy, and surgical therapy) the survival rate of OSCC patients has remained less than 60% [4,5]. A fundamental barrier in improving the survival of OSCC patients is the fact that these malignancies often remain undetected until the later stages. In this regard, it was reported that a severalmonth delay in diagnosis could reduce the chance of survival from 80% to 40% [6]. In order to prevent the high OSCC-related mortality rate, recent attention has been focused on identifying potential diagnostic molecular markers (e.g., cell cycle regulators) that might represent biological predictors of oral cancer [7]. OSCC has been linked to several risk factors, including various bacterial pathogens [8], which might be useful for detecting OSCC
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