Salivary glands tumors account for approximately 3% of all tumors in the head and neck region. This type of tumors is highly variable in clinical manifestation and histology. The World Health Organization (WHO) classifies 22 types of malignant and 11 types of benign tumors of the salivary glands. The multiplicity of types of such tumors poses enormous problems for diagnosis, which is largely based on imaging (ultrasound, magnetic resonance imaging) and fine-needle aspiration biopsy; however, the final diagnosis is based on the histopathological examination of the removed tumor tissue. Saliva as the product of salivary glands thus appears to be an ideal material for the possible search for biomarkers.
The saliva peptidome of 24 patients diagnosed with salivary gland tumor was analyzed. For 11 patients, samples of tumor tissue as well as healthy tissue were also available; tissue samples were obtained during surgical removal of tumors. The control group consisted of 8 saliva samples from healthy subjects and data obtained from the PRIDE repository (PXD020211) on saliva samples from 23 patients diagnosed with oral squamous cell carcinoma (cancer of the head and neck region other than salivary gland tumors). More than a hundred unique peptides found only in the saliva of patients with salivary gland tumors were identified. However, none of these peptides was identified in more than two-three samples. Perhaps the lack of identification of universal markers is related to the significant heterogeneity of the tumors studied.
In our research group, we developed a bioinformatics tool (AliceDB) to identify natural amino acid sequence variants. In each sample (saliva is not very rich in proteins), from a few to a dozen natural variants of various proteins were potentially identified. We are currently at the stage of analyzing the occurrence of natural variants, especially those variants that may be markers of the cancer lesions under study. For example, to our surprise in about 60% of the samples (samples from all analysed groups) we identified peptides containing the R49H variant for products of the PRB4 gene encoding Basic salivary proline-rich protein 4. The result is all the more surprising because gnomic data suggest that this type of variant is quite rare (less than 0.1% of population - GenBank-NCBI). The identified peptides containing the above-mentioned variant cannot be part of any other protein (from any species) whose sequence is deposited in the UNIPROT database.
Therefore, we speculate that the identified peptide is unlikely to be derived from oral bacterial flora or food debris, and is a rather non-canonical product of the PRB4 gene. We hope that, further detailed analysis of the protein sequence variants will enable the identification of salivary gland tumor markers, which is the goal of this project.