Paper Info
Title
Extensive Decoupling of Metabolic Genes in Cancer.
Abstract
Tumorigenesis requires the re-organization of metabolism to support malignant proliferation. We examine how the altered metabolism of cancer cells is reflected in the rewiring of co-expression patterns among metabolic genes. Focusing on breast and clear-cell kidney tumors, we report the existence of key metabolic genes which act as hubs of differential co-expression, showing significantly different co-regulation patterns between normal and tumor states. We compare our findings to those from classical differential expression analysis, and counterintuitively observe that the extent of a gene's differential co-expression only weakly correlates with its differential expression, suggesting that the two measures probe different features of metabolism. Focusing on this discrepancy, we use changes in co-expression patterns to highlight the apparent loss of regulation by the transcription factor HNF4A in clear cell renal cell carcinoma, despite no differential expression of HNF4A. Finally, we aggregate the results of differential co-expression analysis into a Pan-Cancer analysis across seven distinct cancer types to identify pairs of metabolic genes which may be recurrently dysregulated. Among our results is a cluster of four genes, all components of the mitochondrial electron transport chain, which show significant loss of co-expression in tumor tissue, pointing to potential mitochondrial dysfunction in these tumor types.
Year
DOI
Venue
2015
10.1371/journal.pcbi.1004176
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
Cancer metabolism,Gene Expression,Differential Co-expression
Carcinogenesis,Gene,Cancer cell,Biology,Mitochondrion,Clear cell renal cell carcinoma,Bioinformatics,Genetics,Gene expression profiling,Cancer,Transcription factor
Journal
Volume
Issue
Citations 
11
5
2
PageRank 
References 
Authors
0.37
12
2
Name
Order
Citations
PageRank
Ed Reznik1233.07
Chris Sander220.37