Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related deaths worldwide and has no effective screening strategy. It arises as a primary lesion originating in any of the oral tissues, or as an extension from a neighboring anatomic structure, and can also arise by metastasis from a distant site of origin. Use of tobacco is one of the predominant risk factors for the development of oral cancer. Currently, there are no markers identifying individuals at a higher risk of developing the disease. Therefore, successful identification and translation of candidate molecules could aid in clinical knowledge.
Recent developments in quantitative proteomics have enabled the discovery of blood-based markers for various cancers. In this study, we employed a tandem mass tag (TMT)-based quantitative proteomics approach to study alterations in serum proteomes of oral cancer patients with tobacco habit as compared to healthy individuals. The analysis on Fourier transform Orbitrap Fusion Tribrid mass spectrometer resulted in the identification of ~1200 proteins of which ~200 proteins found to be dysregulated (p-value ≤ 0.05). Enrichment analysis revealed significant perturbation of signaling pathways pertaining to angiogenesis, metabolic process, immune response and regulation of MAPK cascade pathways. Proteins mediating these pathways including ADA2, CLEC3B, PDLIM1, PGLYRP2, and NKPD1 were significantly altered in OSCC patients who are tobacco users.
In summary, the current study identified several serum-based proteins, of which ADA2, SERPINA6, and SERPINF1 are few key molecules altered in OSCC patients with tobacco use and may be potential biomarkers to diagnose and monitor the disease. This needs to be validated in larger cohorts to help identify individuals who are at higher risk of developing oral cancer.