Using imaging mass cytometry to map leukoplakia microenvironment proteins predictors of transformation to oral cancer

• Grant number: 23/02756-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 31, 2023
• End date: July 30, 2024
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Adriana Franco Paes Leme
• Grantee: Erison Santana dos Santos
• Supervisor: Renata Ferrarotto
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
• Institution abroad: University of Texas MD Anderson Cancer Center (MD Anderson), United States
• Associated to the scholarship: 22/04490-1 - Validation of markers of malignant transformation into oral squamous cell carcinoma using imaging mass cytometry and targeted proteomics, BP.DR

Abstract

The diagnosis of oral squamous cell carcinoma (OSCC) is commonly realized in advanced stages, which leads to invasive therapies, decreased survival rates, and a worse prognosis. Even in São Paulo, the most developed state of Brazil, more than 70% of patients are diagnosed with stages III/IV disease. OSCC onset may be preceded by a group of oral disorders, such as oral leukoplakia (OL) and proliferative oral leukoplakia (PVL), that present an increased risk of malignant transformation to OSCC. However, the molecular underlying of this biological process is unclear. Recently, we successfully used liquid biopsy of tear fluids from patients with OL, PVL, and OSCC to discover a panel of proteins that may predict the malignant transformation to OSCC. Combining different proteomic data analysis strategies, we identified 24 proteins that correlated with clinicopathological features associated with malignant progression, such as epithelial dysplasia, excessive alcohol consumption, alterations of the immune system, lymph nodal metastasis and clinical stages. However, how these proteins participate in the malignant progression is still uncertain. We hypothesized that the proteins identified in tear fluids can modulate the components of the microenvironment of OL and PVL, leading to OSCC onset. The main goal of this internship is to use imaging single-cell analysis and spatial proteomics to revels the acquisition of malignant phenotype of OL and PVL to OSCC in an independent cohort of patients. Understanding the underlying process of malignant transformation within the microenvironment can pave ways to predict of malignant transformation foremost later diagnosis, improving prognosis and survival rates. (AU)