Extensive decoupling of metabolic genes in cancer Journal Article
| Authors: | Reznik, E.; Sander, C. |
| Article 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. © 2015 Reznik, Sander. |
| Keywords: | unclassified drug; protein function; protein motif; cell proliferation; breast cancer; gene expression; brca1 protein; kidney carcinoma; carcinogenesis; lung adenocarcinoma; malignant neoplastic disease; liver cancer; thyroid cancer; prostate adenocarcinoma; catalysis; aminotransferase; malignant transformation; cell metabolism; lipogenesis; transcription factor nfat; genetic linkage; phosphoserine; lymphoid enhancer factor 1; head and neck squamous cell carcinoma; 2 oxoglutaric acid; disorders of mitochondrial functions; respiratory chain; human; article; hepatocyte nuclear factor 4alpha; hepatocyte nuclear factor 4; acetyl coenzyme a acetyltransferase; beta glucosidase; cysteine dioxygenase; estrogen related receptor alpha; glycine aminotransferase; glycogen phosphorylase; phosphoserine aminotransferase 1; transcription factor pax4 |
| Journal Title: | PLoS Computational Biology |
| Volume: | 11 |
| Issue: | 5 |
| ISSN: | 1553-7358 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-05-11 |
| Start Page: | e1004176 |
| Language: | English |
| DOI: | 10.1371/journal.pcbi.1004176 |
| PROVIDER: | scopus |
| PMCID: | PMC4427321 |
| PUBMED: | 25961905 |
| DOI/URL: | |
| Notes: | Export Date: 2 July 2015 -- Source: Scopus |
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