The nucleolar related protein Dyskerin pseudouridine 1 synthase 1 (DKC1) predicts poor prognosis in breast cancer

Elsharawy, Khloud A.; Mohammed, Omar J.; Aleskandarany, Mohammed A.; Hyder, Ayman; El-Gammal, Hekmat L.; -Dobara, Abou; Green, Andrew R.; Dalton, Leslie W.; Rakha, Emad A.

Abstract

Background

Hypertrophy of the nucleolus is a distinctive cytological feature of malignant cells and corresponds to aggressive behaviour. This study aimed to identify the key gene associated with nucleolar prominence (NP) in breast cancer (BC) and determine its prognostic significance.

Methods

From The Cancer Genome Atlas (TCGA) cohort, digital whole slide images identified cancers having NP served as label and an information theory algorithm was applied to find which mRNA gene best explained NP. Dyskerin Pseudouridine Synthase 1 (DKC1) was identified. DKC1 expression was assessed using mRNA data of Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1980) and TCGA (n = 855). DKC1 protein expression was assessed using immunohistochemistry in Nottingham BC cohort (n = 943).

Results

Nuclear and nucleolar expressions of DKC1 protein were significantly associated with higher tumour grade (p [less than] 0.0001), high nucleolar score (p [less than] 0.001) and poor Nottingham Prognostic Index (p [less than] 0.0001). High DKC1 expression was associated with shorter BC-specific survival (BCSS). In multivariate analysis, DKC1 mRNA and protein expressions were independent risk factors for BCSS (p [less than] 0.01).

Conclusion

DKC1 expression is strongly correlated with NP and its overexpression in BC is associated with unfavourable clinicopathological characteristics and poor outcome. This has been a detailed example in the correlation of phenotype with genotype.

Citation

Elsharawy, K. A., Mohammed, O. J., Aleskandarany, M. A., Hyder, A., El-Gammal, H. L., -Dobara, A., Green, A. R., Dalton, L. W., & Rakha, E. A. (2020). The nucleolar related protein Dyskerin pseudouridine 1 synthase 1 (DKC1) predicts poor prognosis in breast cancer. British Journal of Cancer, 123, 1543–1552. https://doi.org/10.1038/s41416-020-01045-7

• Journal Article Type: Article
• Acceptance Date: Aug 13, 2020
• Online Publication Date: Sep 1, 2020
• Publication Date: Sep 1, 2020
• Deposit Date: Sep 2, 2020
• Publicly Available Date: Mar 2, 2021
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 123
• Pages: 1543–1552
• DOI: https://doi.org/10.1038/s41416-020-01045-7
• Public URL: https://nottingham-repository.worktribe.com/output/4873650
• Publisher URL: https://www.nature.com/articles/s41416-020-01045-7