## 6 Biomarker Detection
### Proteomic-Based Biomarkers  
Proteomics is a promising technique for identifying new biomarkers with prognostic and diagnostic potential [72; 73]. The identification of new biomarkers in OSCC may be aided by analyzing cellular entire protein complements or biofluids. A key feature of various research studies [74] is a saliva proteome profiling study based on patient categorization. Tests have been performed to see how much protein is found in samples of OSCC and healthy tissue, as well as in other in vitro systems for this disease [75]. A lot of proteins that affect cellular functions and structure, cellular adhesion, or cell migration, and proteins that make cancer more likely were found to be changed in studies [76; 77]. When researchers looked at the plasma proteome of mice with OSCC, they found that haptoglobin and the precursor of apolipoprotein A1 have both been upregulated. The expression of haptoglobin plasma in humans showed that there was a strong connection between increasing levels of haptoglobin and the clinical stages of OSCC. This suggests that haptoglobin could be used as a plasma diagnostic marker for identification of OSCC patients [78].  
A SELDI-TOF Protein Chip technology was used to screen saliva proteins from pre- and post-treatment OSCC tests to find 26 candidates with different patterns in their saliva that could be linked to the disease. The investigation found a shortened cystatin SA-I of 14 kDa in pre-treatment saliva samples, with a deletion of three amino acids at the N-terminal end [79]. Protein Chip analysis could be a good way to screen for OSCC at an early stage, and truncated cystatin SA-I could be a good tumor prognostic marker for OSCC. Transglutaminase 3 (TGM3) downregulation was linked to OSCC histological differentiation loss in another study [80]. There were 52 proteins that had statistical significance, so a comparative proteomics study found a group of eight proteins that were more or less common in different people. Annexin A8, Peroxiredoxin-2, and Tyrosine Kinase have been observed in both diabetes and OSCC, and they were thought to be possible biomarkers for OSCC diagnosis because they were found in both [81]. A mass spectrometer study of saliva from people with cancer and healthy people found 213 new proteins. The salivary biomarkers Profilin, Cofilin, S100A9, and MMP9 have all been found to be linked to head and neck cancer. Vimentin has been linked to the epithelial-mesenchymal transition and metastasis of head and neck cancer [82].  
Exosomes are endocytic membrane bound vesicles with nucleic acids (DNA and RNA) inside their lumen that originate from the cell's cytoplasm. They are secreted in large amounts and are found abundantly in bodily fluids. Exosome surface proteins can function as antigens for certain antibodies, which can then be utilized to isolate desired exosomes via affinity-based approaches. Exosomes generated from cancer are said to reflect the tumor microenvironment and can thus be employed as a biomarker for tumor identification [83; 84]. The lipid bilayer of exosomes is made up of cholesterol, phosphatidylinositolserine, and ceramide, as well as trans-membrane receptors, proteolytic enzymes, tetraspannins, and adhesion molecules. Some proteins that are linked to cancer are also very common on the exterior of exosomes, thus making them useful as markers for differentiating between different types of cancer. Proteins such as HER2, LMP1, and MUC18 can be used to make biosensors that can detect total exosomes.