Dept. of Medical Informatics and Clinical Epidemiology
Oregon Health & Science University
Colorectal cancer is one of the most pervasive and deadly diseases in the world today. Although heavily studied with a wealth of available scientific data, little research has been directed at uniting the various biological metrics to test for novel genetic signals and markers that may be otherwise overlooked in singular studies. The current thesis addresses this by utilizing a combined, multi-method analysis to examine biological archetypes in colorectal adenomas by evaluating patterns of differential expression, co-expression disruption, protein product interaction, and transcription factor binding across an available selection of cancerous cell lines, patient colorectal adenomas and normal patient mucosa. First, an aggregate evaluation was used to identify disruptions in co-expression resulting from adenocarcinoma development in addition to differential gene regulation. The resulting gene expression patterns were compared against the chromatin occupancy of Î²-catenin, a key molecule in the canonical Wnt pathway. The results of this pooled analysis were overlain onto a protein-protein interaction network derived from the Wnt pathway to identify genes of interest matching multiple categories of biological metrics. A number of genes identified in the empirical network were further categorized based on their functional ontologies and examined for their prospective role in either the treatment or detection of adenocarcinomas. In addition to isolating a number of potentially intriguing markers, this study also represents a novel method of disease assessment with applicability in conditions beyond colon cancer.
School of Medicine
Murchison, Charles F., "The inteactions of differently expressed genes directly targeted by Wnt\[beta]-catenin signaling : implications for colorectal carcinogenesis" (2010). Scholar Archive. 598.