Prognostic Significance of KN Motif and Ankyrin Repeat Domains 1 (KANK1) in Invasive Breast Cancer

Kariri, Yousif A; Joseph, Chitra; Kurozumi, Sasagu; Toss, Michael S; Alsaleem, Mansour; Raafat, Sara; Mongan, Nigel P; Aleskandarany, Mohammed A; Green, Andrew R; Rakha, Emad A

Abstract

Background: KN Motif and Ankyrin Repeat Domains 1 (KANK1) plays an important role in cytoskeleton maintenance and contributes to the regulation of cell proliferation, adhesion and apoptosis. KANK1 is involved in progression of a variety of solid tumours, however, its role in invasive breast cancer (BC) remains unknown. This study aims to evaluate the clinicopathological and prognostic value of KANK1 expression in operable BC.
Methods: KANK1 expression was assessed at the transcriptomic level using multiple BC cohorts; the Molecular Taxonomy of BC International Consortium cohort (METABRIC; n=1980), The Cancer Genome Atlas BC cohort (TCGA; n=949) and the publicly available BC transcriptomic data hosted by BC Gene-Expression Miner (bc- GenExMiner v4.0) and Kaplan Meier-plotter?. The Nottingham BC cohort (n=1500) prepared as tissue microarrays was used to assess KANK1 protein expression using immunohistochemistry (IHC). The association between clinicopathological variables and patient outcome was investigated.
Results: In the METABRIC cohort, high expression of KANK1 mRNA was associated with characteristics of good prognosis including lower grade, absence of lymphovascular invasion and HER2 negativity (all; p

• Journal Article Type: Article
• Acceptance Date: Oct 1, 2019
• Online Publication Date: Nov 2, 2019
• Publication Date: 2020-01
• Deposit Date: Oct 2, 2019
• Publicly Available Date: Nov 12, 2019
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 179
• Issue: 2
• Pages: 349–357
• DOI: https://doi.org/10.1007/s10549-019-05466-8
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/2735072
• Publisher URL: https://link.springer.com/article/10.1007%2Fs10549-019-05466-8
• Additional Information: Received: 24 September 2019; Accepted: 1 October 2019; First Online: 2 November 2019; : ; : All authors declare that they have no conflict of interest.; : This work obtained ethics approval to use the human tissue samples by the North West–Greater Manchester Central Research Ethics Committee under the title: Nottingham Health Science Biobank (NHSB), reference number 15/NW/0685. Informed consent was obtained from all individuals prior to surgery to use their tissue materials in research. This study was performed according to the REMARK guidelines for tumour prognostic studies.; : This article does not contain any studies with human participants or animals performed by any of the authors.