Avaliação de marcadores de hipóxia e proteômica em neoplasias benignas e malignas de glândula salivar

Abstract

Malignant salivary gland neoplasms account for approximately 3%-6% of all head and neck cancers worldwide and constitute a large, histologically diverse group. These neoplasms usually have poor responses to chemotherapy and radiotherapy treatments. In general, well-oxygenated malignancies show a better response to radiation and are therefore more radiosensitive than poorly oxygenated ones. Hypoxia is a powerful cellular stimulus that induces the signaling pathway dedicated to environmental adaptation and is associated with poor prognosis in cancer. The main protein of the hypoxia pathway is the hypoxia-induced factor (HIF-1α), which is a transcription factor that targets a series of adaptation genes under hypoxic conditions, including miR-210, which is a microRNA up-regulated in the hypoxic microenvironment. This doctoral thesis aimed to investigate the hypoxia markers HIF-1α and miR-210 through immunohistochemistry and real-time polymerase chain reaction (qPCR) in benign and malignant salivary gland neoplasms, in addition to looking for other tumor markers in these neoplasms, through proteomic study. As a result, similar expression levels of HIF 1α and miR-210 were observed between benign and malignant salivary gland neoplasms, as well as no significant differences were observed in the expression of miR-210 between salivary gland neoplasms and non-neoplastic salivary tissue. . The proteome associated with the analysis with the Gene Expression Omnibus (GEO) database showed that the protein annexin A2 (ANXA-2) was the most expressed among malignant salivary gland neoplasms. We consider that the hypoxia markers HIF-1α and miR-210 do not seem to differentiate between benign and malignant salivary gland neoplasms. We also consider that ANXA-2 may be a tumor marker of interest in malignant salivary gland neoplasms. The low number of samples is a limitation of the study.