WDR5 Expression Is Prognostic of Breast Cancer Outcome

• Published in: PloS one Vol. 10; no. 9; p. e0124964
• Main Authors: Dai, Xiaofeng, Guo, Wenwen, Zhan, Chunjun, Liu, Xiuxia, Bai, Zhonghu, Yang, Yankun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.09.2015; Public Library of Science (PLoS)
• Subjects: Anthracycline; Biotechnology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cell cycle; Cell Line, Tumor; Cell proliferation; Cell Survival; Chemotherapy; Cytokines; Datasets; DNA damage; Doxorubicin; Engineering; Epigenetics; Female; Fermentation; Gene expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene regulation; Gene Regulatory Networks; Genes; Genetic aspects; Genomes; Genomics; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Humans; Intracellular Signaling Peptides and Proteins; Kaplan-Meier Estimate; Laboratories; Leukemia; MCF-7 Cells; Medical prognosis; Metastasis; Mutation; Overexpression; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Prognosis; Prostate cancer; Quantitative Trait Loci - genetics; Reproducibility of Results; Single-nucleotide polymorphism; Survival; Survival analysis; Treatment Outcome; Tumor proteins; Tumors; China; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124964

WDR5 is a core component of the human mixed lineage leukemia-2 complex, which plays central roles in ER positive tumour cells and is a major driver of androgen-dependent prostate cancer cell proliferation. Given the similarities between breast and prostate cancers, we explore the potential prognostic value of WDR5 gene expression on breast cancer survival. Our findings reveal that WDR5 over-expression is associated with poor breast cancer clinical outcome in three gene expression data sets and BreastMark. The eQTL analysis reveals 130 trans-eQTL SNPs whose genes mapped with statistical significance are significantly associated with patient survival. These genes together with WDR5 are enriched with "cellular development, gene expression, cell cycle" signallings. Knocking down WDR5 in MCF7 dramatically decreases cell viability, but does not alter tumour cell response to doxorubicin. Our study reveals the prognostic value of WDR5 expression in breast cancer which is under long-range regulation of genes involved in cell cycle, and anthracycline could be coupled with treatments targeting WDR5 once such a regimen is available.