Date of Award

Spring 5-2019

Degree Name

Master of Public Health (MPH)

Advisor(s)

R. SUE DAY, MS, PHD

Second Advisor

LINDA PILLER, MD, MPH

Abstract

Cellular immune response, specifically tumor infiltrating lymphocytes (TILs), has been correlated to survival in epithelial ovarian cancer; however, specific gene expression patterns for this response remain poorly understood. The objective of this research was to investigate the prognostic and biologic significance of immune-related gene expression in high grade serous ovarian cancer (HGSOC). To do so, a panel of immune related gene expression was evaluated in HGSOC utilizing The Cancer Genome Atlas (TCGA) and validated in an independent cohort of ovarian tumors. Based on the strong association with survival, the cohort was grouped into LCK (lymphocyte specific tyrosine kinase) high and non-LCK high tumors and profiles of gene expression and clinical information were obtained. We demonstrate that mRNA upregulation of LCK was correlated with the strongest improvement in survival of the genes investigated. When compared to previously validated metrics such as cytolytic activity score (CYT), LCK proved to be a more discerning prognosticator across tumor types available in the TCGA. In ovarian cancer, correlated gene enrichments were notable for chemokine and immunoglobin complex related genes, ie B cell related transcripts. Therefore, this research shows that LCK is a biomarker of prognostic and biological importance, potentially due to its ability to capture the genomic signature of cooperative T and B cell interaction. This provides essential support for further investigation into the role of tumor infiltrating B cells (TIL-B) and tertiary lymphoid structures (TLS), from which insights into this cooperation can be drawn. As ovarian cancer is the leading cause of death from gynecologic malignancy, such insights have the potential to not only offer important prognostic information but also may provide novel therapeutic approaches to the treatment of this deadly disease.

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