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

• Published in: Breast cancer research and treatment Vol. 179; no. 2; pp. 349 - 357
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-01-2020; Springer; Springer Nature B.V
• Subjects: Ankyrins; Apoptosis; Breast cancer; Cancer; Cancer research; Cell proliferation; Cytoskeleton; DNA microarrays; ErbB-2 protein; Gene expression; Genetic aspects; Genomes; Genomics; Immunohistochemistry; Invasiveness; Medical colleges; Medical prognosis; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metastases; Metastasis; Oncology; Preclinical Study; Prognosis; Protein expression; RNA; Solid tumors; Invasive breast cancer; KANK1; Prognostic; Lymphovascular invasion
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-019-05466-8

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.