Advisory Committee Chair
Advisory Committee Members
J Bart Rose
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) School of Medicine
Pancreatic Neuroendocrine Tumors (PNETs) are highly heterogeneous neoplasms arising from the hormone-secreting cells of the endocrine pancreas. PNETs are broadly categorized as functional and non-functional based on the presence of symptoms associated with hormone secretion, which occurs in approximately 30% of cases. While functional tumors are all considered for resection because of these symptoms and their associated sequelae, non-functional tumors > 2cm are currently resected based on increased risk of developing metastatic disease. However, this criterion is based on data from predominantly White patients. Recent studies have shown that Black patients have much higher rates of lymph node metastatic disease at tumor sizes under 2cm, indicating that interracial differences in tumor biology may be responsible. Upon evaluating the diversity of genomic studies in PNETs to investigate this further, we found little representation of Black patients and other ethnoracial minority groups. We then discovered differences in the mutation of key genes in PNETs between Black and White patients; among which was MEN1, the most frequently mutated gene in PNETs. Subsequently, we investigated the transcriptome, tumor microenvironment, and prognostic protein biomarkers for differences between Black and White patients. We discovered that numerous genes were differentially expressed between these cohorts, and that multiple differentially expressed genes were associated with clinical outcomes, iv including tumor progression to metastasis and progression-free survival. Furthermore, we found differences in the infiltration of immune cells into tumors between Black and White patients, alongside differences in the expression of multiple previously established prognostic protein biomarkers. These data indicate that a host of molecular influences may indeed be driving racial disparities in PNET clinical outcomes.
Herring, Brendon, "Molecular Influences of Racial Disparities in Pancreatic Neuroendocrine Tumors" (2023). All ETDs from UAB. 425.
Available for download on Sunday, September 01, 2024