High nuclear MSK1 is associated with longer survival in breast cancer patients

Pu, Xuan; Storr, Sarah J.; Ahmad, Narmeen; Rakha, Emad; Green, Andrew R.; Ellis, Ian O.; Martin, Stewart G.

Abstract

Purpose: Mitogen- and stress- activated kinases (MSKs) are important substrates of the mitogen-activated protein kinase (MAPK)-activated protein kinase family. MSK1 and MSK2 are both nuclear serine/threonine protein kinases, with MSK1 being suggested to potentially play a role in breast cancer cell proliferation, cell cycle progression, cell migration, invasion and tumour growth. The aim of the current study was to assess MSK1 protein expression in breast cancer tumour specimens, evaluating its prognostic significance.

Methods: A large cohort of 1902 early stage invasive breast cancer patients was used to explore the expression of MSK1. Protein expression was examined using standard immunohistochemistry on tissue microarrays.

Results: Low MSK1 protein expression was associated with younger age (P=0.004), higher tumour grade (P<0.001), higher Nottingham Prognostic Index scores (P=0.007), negative ER (P<0.001) and PR (P<0.001) status, and with triple-negative (P<0.001) and basal-like (P<0.001) phenotypes. Low MSK1 protein expression was significantly associated with shorter time to distant metastasis (P<0.001), and recurrence (P=0.013) and early death due to breast cancer (P=0.01). This association between high MSK1 expression and improved breast cancer-specific survival was observed in the whole cohort (P=0.009) and in the HER2 negative and non-basal like tumours (P=0.006 and P=0.024, respectively). Multivariate analysis including other prognostic variables indicated that MSK1 is not an independent marker of outcome.

Conclusions: High MSK1 is associated with improved breast cancer-specific survival in early stage invasive breast cancer patients, and has additional prognostic value in HER2 negative and non-basal like disease. Although not an independent marker of outcome we believe such findings, and significant associations with well-established negative prognostic factors (age, grade, Nottingham Prognostic Index, hormone receptor status, time to distant metastasis

Citation

Pu, X., Storr, S. J., Ahmad, N., Rakha, E., Green, A. R., Ellis, I. O., & Martin, S. G. (2018). High nuclear MSK1 is associated with longer survival in breast cancer patients. Journal of Cancer Research and Clinical Oncology, 144(3), https://doi.org/10.1007/s00432-018-2579-7

• Journal Article Type: Article
• Acceptance Date: Jan 6, 2018
• Online Publication Date: Jan 11, 2018
• Publication Date: Mar 30, 2018
• Deposit Date: Jan 9, 2018
• Publicly Available Date: Jan 11, 2018
• Journal: Journal of Cancer Research and Clinical Oncology
• Print ISSN: 0171-5216
• Electronic ISSN: 1432-1335
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 144
• Issue: 3
• DOI: https://doi.org/10.1007/s00432-018-2579-7
• Keywords: Breast cancer; MSK; Breast cancer-specific survival; Biomarker
• Public URL: https://nottingham-repository.worktribe.com/output/922254
• Publisher URL: https://link.springer.com/article/10.1007/s00432-018-2579-7
• Contract Date: Jan 9, 2018