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Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis

Open access
Clarke, Colin, Madden, Stephen F., Doolan, Padraig, Aherne, Sinead T., Joyce, Helena, O’Driscoll, Lorraine, Gallagher, William M., Hennessy, Bryan T., Moriarty, Michael, Crown, John, Kennedy, Susan, Clynes, Martin·2013·Carcinogenesis

Abstract

Weighted gene coexpression network analysis (WGCNA) is a powerful 'guilt-by-association'-based method to extract coexpressed groups of genes from large heterogeneous messenger RNA expression data sets. We have utilized WGCNA to identify 11 coregulated gene clusters across 2342 breast cancer samples from 13 microarray-based gene expression studies. A number of these transcriptional modules were found to be correlated to clinicopathological variables (e.g. tumor grade), survival endpoints for breast cancer as a whole (disease-free survival, distant disease-free survival and overall survival) and also its molecular subtypes (luminal A, luminal B, HER2+ and basal-like). Examples of findings arising from this work include the identification of a cluster of proliferation-related genes that when upregulated correlated to increased tumor grade and were associated with poor survival in general. The prognostic potential of novel genes, for example, ubiquitin-conjugating enzyme E2S (UBE2S) within this group was confirmed in an independent data set. In addition, gene clusters were also associated with survival for breast cancer molecular subtypes including a cluster of genes that was found to correlate with prognosis exclusively for basal-like breast cancer. The upregulation of several single genes within this coexpression cluster, for example, the potassium channel, subfamily K, member 5 (KCNK5) was associated with poor outcome for the basal-like molecular subtype. We have developed an online database to allow user-friendly access to the coexpression patterns and the survival analysis outputs uncovered in this study (available at http://glados.ucd.ie/Coexpression/).

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Metadata

Authors
Clarke, C., Madden, S. F., Doolan, P., Aherne, S. T., Joyce, H., O’Driscoll, L., Gallagher, W. M., Hennessy, B. T., Moriarty, M., Crown, J., Kennedy, S., & Clynes, M.
Venue
Carcinogenesis
Published
2013-06-05
Volume
34
Issue
10
Pages
2300-2308
ISSN
  • 0143-3334 (ISSN-L)
  • 1460-2180
OpenAlex
W2111758831
Cited by
849
References
52
FWCI
5.69
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis. https://app.cochat.ai/papers/10.1093/carcin/bgt208
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Clarke, C., Madden, S. F., Doolan, P., Aherne, S. T., Joyce, H., O’Driscoll, L., Gallagher, W. M., Hennessy, B. T., Moriarty, M., Crown, J., Kennedy, S., & Clynes, M. (2013). Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis. Carcinogenesis. https://doi.org/10.1093/carcin/bgt208

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