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Pathways of Distinction Analysis of Liver Cancer Data: Genetic Differences Between Males and Females
Description
The Pathways of Distinction Analysis (PoDA) program calculates relationships between a given group of genes contained within a pathway, and a disease state. It was used here to investigate liver cancer, and to explore how genetic variability may contribute to the different rates of development of the disease in males and females. The goal of the study was to identify germline variation that differs by sex in hepatocellular carcinoma. Using the program, multiple pathways and genes were identified to have significant differences in their relationship to liver cancer in males and females. In animal studies, the genes which were identified using the PoDA analysis have been shown to impact liver cancer, often with different results for males and females. While these genes are often the focus in animal models, they are absent from current Genome Wide Association Studies (GWAS) catalogs for humans. By working to bridge the results of animal studies and human studies, the results help to identify the causes of liver cancer, and more specifically, the reason the disease affects males at much higher rates. The differences in pathways identified to be significant for the two sexes indicate the germline variance may play sex-specific roles in the development of hepatocellular carcinoma. Additionally, these results reinforce the capacity of the PoDA analysis to identify genes that may be missed by more traditional GWAS methods. This study lays the groundwork for further investigations into the identified genes and pathways, and how they behave differently within males and females.
ContributorsOlson, Erik Jon (Author) / Buetow, Kenneth (Thesis advisor) / Wilson, Melissa (Committee member) / Cartwright, Reed (Committee member) / Arizona State University (Publisher)
Created2021
Description
Glioblastoma multiforme is associated with a very low survival rate and is recognized as the most vicious form of intracranial cancer. The Akt gene pathway has three different isoforms, each of which has a different role in the tumors of GBM. Preliminary data suggests that Akt3 may work to decrease tumorigenicity. A produced image that visualizes the subcellular localization of Akt3 led the author to believe that Akt3 may reduce tumorigenicity by decreasing genomic instability caused by the cancer. To explore this, flow cytometry was performed on GBM cell lines with Akt3v1 over-expression, Akt3v2 over-expression, and a control glioma cell line.
ContributorsGhorayeb, Antoine (Author) / Neisewander, Janet (Thesis director) / Diehnelt, Chris (Committee member) / Moussallem, Suzan (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12