期刊
BRITISH JOURNAL OF CANCER
卷 123, 期 10, 页码 1543-1552出版社
SPRINGERNATURE
DOI: 10.1038/s41416-020-01045-7
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资金
- Breast Cancer Now
- PathLAKE project
- Data to Early Diagnosis and Precision Medicine strand of the government's Industrial Strategy Challenge by UK Research and Innovation (UKRI)
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.DKC1expression 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 < 0.0001), high nucleolar score (p < 0.001) and poor Nottingham Prognostic Index (p < 0.0001). High DKC1 expression was associated with shorter BC-specific survival (BCSS). In multivariate analysis,DKC1mRNA and protein expressions were independent risk factors for BCSS (p < 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.
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