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Dissertation
Multi-omics-based approach to understanding genomic and functional features shared by osteosarcoma and bone metastatic prostate cancer
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2024
DOI:
https://doi.org/10.17918/00010852
Abstract
This research identifies key molecular and epigenetic drivers' cancer growth and proliferation in the skeleton by investigating bone-metastatic prostate cancer and primary osteosarcoma, through the integration of gene expression and methylation data using statistical and machine learning approaches. Aim 1 focused on developing methodologies for analyzing methylation and gene expression data, including the design and analysis of the novel mm285 mouse methylation array. These approaches were applied in Aim 2 to bone-tropic prostate cancer, verifying the inverse relationship between the androgen receptor and the cytokine Interleukin-1beta and identifying differential methylation as a regulatory mechanism. Additional analyses highlighted the role of the chemokine receptor CX3CR1 and compared bone-metastatic prostate adenocarcinoma to neuroendocrine prostate cancer that metastasized to soft tissues. In Aim 3, a random forest (RF) model identified 140 genes differentiating bone metastatic from non-bone metastatic prostate cancers, with 88 showing consistent trends in primary osteosarcoma and 8 linked to significantly worse patient survival. Methylation data revealed 85 CpGs correlated with these genes, including 54 CpGs with positive and 31 with negative correlations, implicating enhancer-mediated activation and methylation-induced repression. These findings highlight critical regulatory elements and provide a foundation for experimental validation of the newly acquired information with the goal of identifying novel therapeutic targets for the treatment of both primary and secondary bone tumor.
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Details
- Title
- Multi-omics-based approach to understanding genomic and functional features shared by osteosarcoma and bone metastatic prostate cancer
- Creators
- Waleed Iqbal
- Contributors
- Alessandro Fatatis (Advisor)Amy Throckmorton (Advisor) - Drexel University, School of Biomedical Engineering, Science, and Health Systems
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- viii, 158 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991022020017104721