Prognostic significance of KN motif and ankyrin repeat domains 1 (KANK1) in invasive breast cancer

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

Research output: Contribution to journalJournal articlepeer-review

7 Scopus citations

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 < 0.001) and with better outcome [p = 0.006, Hazards ratio, (HR) 0.70, 95% CI 0.54–0.91]. High KANK1 protein expression was correlated with smaller tumour size and HER2 negativity, and better outcome in terms of longer breast cancer-specific survival [p = 0.013, HR 0.7, 95% CI 0.536–0.893] and time to distant metastasis [p = 0.033, HR 0.65, 95% CI 0.51–0.819]. Conclusion: These results supported that upregulation of KANK1 works as a tumour suppressor gene in BC and is associated with improved patients’ outcomes.

Original languageEnglish
Pages (from-to)349-357
Number of pages9
JournalBreast Cancer Research and Treatment
Volume179
Issue number2
DOIs
StatePublished - 1 Jan 2020
Externally publishedYes

Keywords

  • Invasive breast cancer
  • KANK1
  • Lymphovascular invasion
  • Prognostic

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