Evaluation of spatial proteomic complexity in air pollution-related lung cancer tumors.

• Grant number: 24/06240-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2025
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Vitor Marcel Faça
• Grantee: Beatriz Pereira de Morais
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The steady increase in non-small cell lung carcinoma (NSCLC) incidence among never-smoked and those exposed to air atmospheric pollutants, specifically fine particulate matter (PM2.5), is a significant cause for concern. Considering that lung cancer, particularly NSCLC, is among the most prevalent cancers worldwide with a low survival rate, it's necessary to comprehend the molecular mechanisms underlying its onset and progression. Despite the known correlation between EGFR mutations and the development of NSCLC in high-risk patients exposed to PM2.5, practical applications related to treatment and biomarkers of tumor progression in these individuals remain poorly understood. Currently, studies have underscored the importance of spatially understanding tumors to evaluate the impact of different tumor regions and the heterogeneous cellular composition. Advances have been made in enhancing the sensitivity of equipment crucial for proteomics studies, such as mass spectrometers, which are now capable of detecting even the protein profile of a single cell. Consequently, it is now feasible to assess protein variability across different tumor regions to comprehend the influence on tumor development and persistence. This is possible through the strategy of laser microdissection and processing of minimal protein amounts, coupled with high-sensitivity equipment. This approach provides an understanding of the implications of EGFR mutations in NSCLC patients and evaluating the epidemiological risk posed by exposure to PM2.5 in individuals who have never been exposed to cigarette toxins. Conducting a spatial proteomics study on samples from such patients facilitates data integration and offers practical insights into the impact of environmental pollution on the deadliest form of cancer. Moreover, it can aid in discussions regarding epidemiological studies aimed at identifying subgroups predisposed to NSCLC due to occupational hazards exposed to PM2.5. Additionally, proteomic assessment enables the identification of new molecular targets and biomarkers with predictive or therapeutic potential through an integrative approach.