Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Pathology and Laboratory Medicine

Supervisor

Shooshtari, Parisa

Affiliation

Children's Health Research Institute, London Health Sciences Centre

2nd Supervisor

Zhang, Qi

Affiliation

London Health Sciences Centre

Co-Supervisor

Abstract

This study aims to understand the molecular processes influencing metastasis speed and invasion patterns in lung cancer brain metastasis. We used the spatial gene expression profiles and histology images from lung and brain tissues of 35 patients. Applying data integration methods, statistical tests, and gene set enrichment revealed three major categories of pathways: immunity, stemness, and metabolism pathways. To investigate invasion patterns, we developed a scoring system to assess tumor growth patterns and labeled the patients accordingly. Matrix factorization and statistical tests were used for relevant gene set discovery. We also examined the interaction between the tumor microenvironment and brain tumors. Our integrative analyses revealed the possible linked factors to be immune response, mitochondrial dysfunction, histone modification, and cellular processes. Overall, the study provides insights into the molecular processes underlying lung cancer brain metastasis and may contribute to the development of strategies to prevent or manage lung cancer brain metastasis.

Summary for Lay Audience

In this research, we aimed to understand how lung cancer spreads to the brain and why it does so at different speeds and in different ways. We studied the genes and tissues of 35 patients with lung cancer that had spread to the brain. By analyzing the data, we found three main groups of biological features that play a role in speed of this process: the immunity, cell division, and metabolism. To investigate the shape in which the cancer cells grow after the spread, we created a scoring system to evaluate how the tumors grow and categorized the patients based on these patterns. We then used advanced statistical methods to identify genes that are important for this spread. We also studied how the environment surrounding the tumor in the brain affects its growth. Our analysis revealed several factors that may contribute to the spread of lung cancer to the brain, including immune response, problems with cell energy production, changes in gene activity, and cellular processes. Overall, this study provides valuable insights into the molecular processes involved in lung cancer spreading to the brain. It may help researchers develop strategies to prevent or better manage this type of metastasis in the future.

Available for download on Friday, August 01, 2025

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