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Table 5 A summary of the function of each salivary protein identified by proteomics in this study, and its association with lichen planus in previous studies

From: Putative salivary protein biomarkers for the diagnosis of oral lichen planus: a case-control study

Protein name Functions Relation of protein to OLP
Serum originating proteins
 Serum albumin Its main function is the regulation of the colloidal osmotic pressure of blood [44]. It also serves as antioxidant agent [45]. In a study of Battino, et al., serum and salivary anti-oxidant proteins including albumin were investigated using analysis kits from Diasys (Germany). No significant differences were observed both in saliva and in serum for the albumin values in OLP patients when compared with the control group. Even if albumin is known as a protein with antioxidant properties [46]. In another study, the serum albumin levels of OLP patients were within the normal range [47].
 Haptoglobin Haptoglobin captures and combines with free plasma hemoglobin to allow hepatic recycling of heme iron [48].
It is an acute phase reactant which involves in acute phase immune response [49].
It can be detected in the cytoplasm of normal epidermal Langerhans cells and epidermal keratinocytes [50].
In situ hybridization and immuno histochemistry revealed increased haptoglobin expression in keratinocytes of the skin of patients with psoriasis, lichen planus, erythroderma and seborrheic keratosis [21].
 Chain B, crystal structure of fibrinogen fragment D Fibrinogen is a glycoprotein which plays important roles in blood clotting, fibrinolysis, cellular and matric interactions, cell adhesion, inflammatory response, wound healing process and neoplasia [51, 52]. Oral epithelial cells may synthesize and secrete fibrinogen locally in response to proinflammatory mediators [34]. Buajeeb et al. found that using immunofluorescent technic for the detection of fibrinogen in oral lichen planus lesions, 98.5% of tissue specimens were positive for fibrinogen [5]. Other studies also showed presence of fibrinogen in OLP tissue samples using direct immunofluorescence [53, 54].
 Chain C, human complement component C3c C3 plays a central role in the activation of the complement system which mediates local inflammatory process [35]. It is derived from proteolytic degradation of complement C3 and is the major stable conversion product of complement C3 [36]. In one study, component C3 levels were determined in serum and saliva of patients with OLP compared to normal controls. The C3 levels were increased in the OLP group compared with the control group (p < 0.05) [55]. In addition, the presence of C3 deposition as granular and linear patterns in the immunofluorescence has been utilized for the diagnosis of OLP [5].
Gland originating salivary proteins
 Alpha amylase An enzyme that plays a role in the initial digestion of starch [56, 57]. Salivary alpha amylase levels were higher in the morning in patients with OLP compared to control subjects. However, in the evening these levels were lower in OLP subjects than control subjects [58].
 Carbonic anhydrase isozyme VI It has been suggested that carbonic anhydrase VI participates in the maintenance of appropriate pH homeostasis on tooth surfaces as well as in the mucosa of the gastrointestinal canal [59]. No report about this protein in OLP or other related diseases.
 Cystatin S and SA They are proteins belongs to the cystatin superfamily which are cysteine protease inhibitors usually expressed in saliva, tears, urine, and seminal fluid [60]. The S-type cystatins (cystatin S, SN and SA) are mostly found in saliva and share a large intensity of amino acid similarity [61]. They also exert some role in the regulation of saliva calcium and antimicrobial activity [61, 62]. Cathepsin L has been found to be increased in skin specimens of patients with LP [40]. It has been found that salivary cystatin SA can inhibit human cathepsin L [41] which may modulate proteolytic events in OLP.
 Prolactin-induced protein It is a small protein functions in human reproductive and immunological system. It is expressed in several exocrine tissues such as the lacrimal, salivary, and sweat glands [63]. No report about this protein in oral lichen planus or other related diseases.
Tissue/mucosal originating proteins
 Glyceraldehyde-3-phosphate dehydrogenase It is an enzyme that involves in glycolysis. It has recently been reported to be implicated in transcription activation, initiation of apoptosis [64], ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport [65]. No report about this protein in oral lichen planus or other related diseases.
 14–3-3 protein zeta/delta It binds to several proteins and is involved in signal transduction process, regulation of apoptosis and membrane organization [25]. 14–3-3 delta is the phosphorylated form of 14–3-3 zeta [26]. Immunohistochemistry confirmed overexpression of 14–3-3 zeta and theta in premalignant oral lesions and oral squamous cell carcinoma tissues in comparison with normal epithelium [27]. Since oral lichen planus is considered a premalignant lesion, there is a possibility that this protein might be increased in this disease.
14–3-3 zeta/delta has been found to be increased in rheumatoid arthritis, an autoimmune disease [66].
14–3-3 sigma, an isoform of 14–3-3 protein is overexpressed in oral lichen planus on immunohistochemical analysis [67].
 Short-chain specific acyl-CoA dehydrogenase, mitochondrial precursor The short-chain specific acyl-CoA dehydrogenase enzyme catalyzes the first part of fatty acid beta-oxidation by forming a C2-C3 trans-double bond in the fatty acid through dehydrogenation of the flavoenzyme. It is specific to short-chain fatty acids, between C2 and C3-acyl-CoA [68]. When there are defects that result in this enzyme being misfolded, there is an increased production of reactive oxygen species (ROS); the increased ROS forces the mitochondria to undergo fission, and the mitochondrial reticulum takes on a grain-like structure [69]. No report about this protein in oral lichen planus or other related diseases.
 Neutrophil gelatinase-associated lipocalin, NGAL It is a small cationic antimicrobial peptides of epithelial origin [70]. It functions in innate defense against microbial agents [71]. The ligands of NGAL are a variety of bacteria ferric siderophores, which transport iron to bacteria [72]. By taking the iron away from bacteria, NGAL acts as a potent bacteriostatic agent under iron-limiting conditions [73]. NGAL has been found to be a marker for dysregulated keratinocyte differentiation in human skin [74]. Interestingly, NGAL expression was highly increased in psoriasis-like inflammatory disorders such as lichen planus and pityriasis rubula pilaris and skin cancers including keratoacanthoma and squamous cell carcinoma implying that NGAL may be related with the epidermal hyperplasia [22].
 NOL1/NOP2/Sun domain family, member 4 (NSUN4) It is a 5-methylcytosine RNA methyltransferase [75]. Binding of this protein to mitochondrial transcription termination factor 4 (MTERF4) is crucial for ribosome biogenesis which is critical for oxidative phosphorylation capacity. Biogenesis of mammalian mitochondrial ribosomes requires a maturation of both the small and large ribosomal subunit and NSUN4 in complex with MTERF4 is required to assemble the small and large subunits to form a monosome [76]. No report about this protein in oral lichen planus or other related diseases.
 Cytokeratin 9 Cytokeratins are proteins expressed in epithelial cells. It has been used for the markers of epithelial cell differentiation and have been used for determining tumor origin and epithelial cell typing [77]. In a study of Boisnic et al., cytokeratin expression was determined by means of immunohistochemical labeling with use of monoclonal antibodies against cytokeratins and filaggrin and two-dimensional gel electrophoresis. In buccal mucosa lichen planus, the appearance of cytokeratins 1, 2, 10, and 11 coincides with a decrease in cytokeratins 4 and 13 and a moderate increase in cytokeratins 6, 16, 17, and 19. Moreover, this work showed that cytokeratins 1, 2, 10, and 11 and filaggrin are sensitive tools that may help detect early relapse of OLP before clinical exacerbation [78].
 Ig J-chain, partial The J Chain is required for IgM or IgA to be secreted into mucosa [23]. As part of a polymeric immunoglobulin, the J-chain is essential for the formation of dimeric IgA and pentameric IgM molecules and facilitates the secretory component upon excretion by epithelial cells [23]. It also modulates the activation of complement system [23]. No report directly investigate the role of IgJ in OLP. However, Lopez-Jornet has reported significantly increased levels of salivary IgA in patients with OLP compared to normal control [8]. In addition, there is a study indicated the increase level of IgJ mRNA in oral dysplastic lesions [79].