Abstract
BackgroundWeight loss may decrease risk of colorectal cancer in obese individuals, yet its effect in the colorectum is not well understood. We used integrative network modeling, Passing Attributes between Networks for Data Assimilation, to estimate transcriptional regulatory network models from mRNA expression levels from rectal mucosa biopsies measured pre- and post-weight loss in 10 obese, pre-menopausal women. ResultsWe identified significantly greater regulatory targeting of glucose transport pathways in the post-weight loss regulatory network, including “regulation of glucose transport” (FDR=0.02), “hexose transport” (FDR=0.06), “glucose transport” (FDR=0.06) and “monosaccharide transport” (FDR=0.08). These findings were not evident by gene expression analysis alone. Network analysis also suggested a regulatory switch from NFΚB1 to MAX control of MYC post-weight loss. ConclusionsThese network-based results expand upon standard gene expression analysis by providing evidence for a potential mechanistic alteration caused by weight loss.
Highlights
Obesity occurs in over one third of the American population and is associated with increased risk of colorectal cancer [1,2]
These network-based results expand upon standard gene expression analysis by providing evidence for a potential mechanistic alteration caused by weight loss
We used Passing Attributes between Networks for Data Assimilation (PANDA) to build network models of the gene regulatory structure by combining transcription factor motif information with gene expression data from paired mucosal biopsies collected from 10 pre-menopausal women both before and after weight loss
Summary
Obesity occurs in over one third of the American population and is associated with increased risk of colorectal cancer [1,2] It is not clear if one must be of normal weight throughout life to be protected against colorectal cancer or if weight loss decreases risk in obese individuals. Song, et al [8] observed a significant 64% increased risk for colorectal cancer among men who gained ≥20kg in adulthood versus weight stable men, and a trend for a negative association between adult weight loss and colorectal cancer risk among men. Weight loss may decrease risk of colorectal cancer in obese individuals, yet its effect in the colorectum is not well understood. We used integrative network modeling, Passing Attributes between Networks for Data Assimilation, to estimate transcriptional regulatory network models from mRNA expression levels from rectal mucosa biopsies measured pre- and post-weight loss in 10 obese, pre-menopausal women
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