Dados do Resumo

Título

Investigation of the proteomic profile in benign and malignant paragangliomas of the head and neck

Introdução

Paragangliomas (PGLs) are a rare type of neuroendocrine neoplasm that account for up to 0.5% of all head and neck tumors. Head and neck paragangliomas originate in extra-adrenal paraganglia and rarely have endocrine activity. The most common type of PGL is the carotid body and corresponds to up to 75% of cases. They are mostly benign neoplasms and about 10% are reported as malignant. However, there are no biomarkers that can predict malignant behavior in primary tumors.

Objetivo

The aim of this study is the determination of a proteomic profile of benign and malignant PGLs and its relationship with clinical, pathological and demographic characteristics. Selection of targets for validation by immunohistochemistry and analysis of protein-protein interaction networks and metabolic pathways of the targets.

Métodos

Twenty-four paraffin-embedded PGL samples were selected: 8 malignant, 11 benign, and 5 multicentric, from the A.C.Camargo Cancer Center's Pathology Department. Patients underwent surgery between 2000 and 2020. Samples will be deparaffinized, followed by protein isolation and digestion for mass spectrometry analysis. Data will be processed using MaxQuant with the Human UniProt database for protein quantification and identification. Selected targets will be validated by immunohistochemistry, with descriptive and semi-quantitative analysis. Protein-protein interaction networks and metabolic pathways will be analyzed using Cytoscape and STRING. Statistical analysis comparing the proteomic profile with clinical, demographic, and pathological characteristics will be conducted using the chi-square test in SPSS. The study was approved by the Research Ethics Committee (protocol 2837/20).

Resultados

The determination of a discriminating proteomic profiles between benign and malignant PGL samples, with validation of the selected targets, identifying potential biomarkers of malignancy in primary tumors. This will facilitate diagnosis and allow the targeting of patients to more specific and personalized therapies according to the degree of disease aggressiveness. In addition, it is expected to identify the protein-protein interaction networks and metabolic pathways involved in the development of PGLs through Cytoscape and STRING, providing a better understanding of the molecular bases of these lesions.

Conclusões

Liquid chromatography-mass spectrometry is robust technique for identifying potential biomarkers. Target validation by immunohistochemistry ensures the accuracy of biomarkers, while in silico analysis of protein-protein interactions and metabolic pathways with Cytoscape and STRING provides detailed insight into the molecular basis of PGLs. These techniques might provide early and less invasive diagnosis and personalized therapies, improving patients’ prognosis and quality of life.

Palavras Chave

PARAGANGLIOMAS; MASS SPECTROMETRY; IMMUNOHISTOCHEMISTRY