Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes

Joseph, Chitra; Macnamara, Olivia; Craze, Madeleine; Russell, Roslin; Provenzano, Elena; Nolan, Christopher C.; Diez-Rodriguez, Maria; Sonbul, Sultan N.; Aleskandarany, Mohammed A.; Green, Andrew R.; Rakha, Emad A.; Ellis, Ian O.; Mukherjee, Abhik

Abstract

Background: Mediator complex (MED) proteins have a key role in transcriptional regulation, some interacting with the oestrogen receptor (ER). Interrogation of the METABRIC cohort suggested that MED7 may regulate lymphovascular invasion (LVI). Thus MED7 expression was assessed in large breast cancer (BC) cohorts to determine clinicopathological significance.
Methods: MED7 gene expression was investigated in the METABRIC cohort (n = 1980) and externally validated using bc-GenExMiner v4.0. Immunohistochemical expression was assessed in the Nottingham primary BC series (n = 1280). Associations with clinicopathological variables and patient outcome were evaluated.
Results: High MED7 mRNA and protein expression was associated with good prognostic factors: low grade, smaller tumour size, good NPI, positive hormone receptor status (p < 0.001), and negative LVI (p = 0.04) status. Higher MED7 protein expression was associated with improved BC-specific survival within the whole cohort and ER+/luminal subgroup. Pooled MED7 gene expression data in the external validation cohort confirmed association with better survival, corroborating with the protein expression. On multivariate analysis, MED7 protein was independently predictive of longer BC-specific survival in the whole cohort and Luminal A subtype (p < 0.001).
Conclusions: MED7 is an important prognostic marker in BC, particularly in ER+luminal subtypes, associated with improved survival and warrants future functional analysis.

Citation

Joseph, C., Macnamara, O., Craze, M., Russell, R., Provenzano, E., Nolan, C. C., Diez-Rodriguez, M., Sonbul, S. N., Aleskandarany, M. A., Green, A. R., Rakha, E. A., Ellis, I. O., & Mukherjee, A. (in press). Mediator complex (MED) 7: a biomarker associated with good prognosis in invasive breast cancer, especially ER+ luminal subtypes. British Journal of Cancer, https://doi.org/10.1038/s41416-018-0041-x

• Journal Article Type: Article
• Acceptance Date: Jan 30, 2018
• Online Publication Date: Mar 28, 2018
• Deposit Date: Apr 16, 2018
• Publicly Available Date: Mar 29, 2019
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1038/s41416-018-0041-x
• Public URL: https://nottingham-repository.worktribe.com/output/921886
• Publisher URL: https://www.nature.com/articles/s41416-018-0041-x
• Contract Date: Apr 16, 2018