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Proteolytic profile analysis in high-grade cervical intraepithelial lesions in HPV infected patients

Grant number: 19/25900-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2020
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Katiuchia Uzzun Sales
Grantee:Vitor de Moura Arrais
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Cervical carcinoma has a high incidence in Brazil and worldwide. Currently, despite all the advances in the area and, due to its prevalence and severity, this condition is considered a public health problem. In 2018 alone, the National Cancer Institute (INCA) estimated 16,370 new cases of this disease in Brazil. This carcinoma develops by integrating Human Papillomavirus (HPV) oncogenes into cervical epithelial cell DNA, inducing a gradual transformation of the normal mucosa into carcinoma. Progress of carcinoma in situ to carcinoma invasion is associated, among other reasons, with a dysregulation in protease expression. Proteases are enzymes that break down peptide bonds between amino acids in proteins, this makes the contributors to the process of tumor invasion and, consequently, metastasis. In this sense, a serine protease matriptase, for example, contributes to cervical carcinoma by activating the PI3K-Akt-mTOR carcinogenic pathway. Preliminary results from our laboratory pointed to the imbalance of other serine proteases, such as kallikrein 5 (KLK5) and kallikrein 7 (KLK7), in premalignant lesions (high-grade intraepithelial lesions) of the uterus. Thus, the main objective of this study is to analyze and modify the proteolytic profile of patients with high cervical intraepithelial lesions; by expanding the number of participants recruited for the clinical study and quantifying serine proteases: matriptase, KLK5 and KLK7, as well as serine protease inhibitors: HAI-1, HAI-2 (cognitive inhibitors of matriptase) and LEKTI (cognitive inhibitor KLK5 and KLK7), in biopsies of lesions and normal tissues from these patients. The selected results allow to analyze and associate the proteolytic profile model to the cellular transformation caused by HPV, besides defining a new perspective for the prognosis of these lesions. (AU)