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The nucleolar-related protein Dyskerin pseudouridine synthase 1 (DKC1) predicts poor prognosis in breast cancer
by
Hyder, Ayman
, Abou-Dobara, Mohamed I.
, Rakha, Emad A.
, El-Gammal, Hekmat L.
, Green, Andrew R.
, Dalton, Leslie W.
, Aleskandarany, Mohammed A.
, Mohammed, Omar J.
, Elsharawy, Khloud A.
in
631/67/1347
/ 692/4028
/ Adult
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Biomarkers, Tumor - physiology
/ Biomedical and Life Sciences
/ Biomedicine
/ Breast cancer
/ Breast Neoplasms - diagnosis
/ Breast Neoplasms - genetics
/ Breast Neoplasms - mortality
/ Breast Neoplasms - therapy
/ Cancer Research
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cell Cycle Proteins - physiology
/ Cohort Studies
/ Datasets as Topic
/ Drug Resistance
/ Epidemiology
/ Female
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Genotypes
/ Humans
/ Hypertrophy
/ Immunohistochemistry
/ Information theory
/ Medical prognosis
/ Middle Aged
/ Molecular Medicine
/ mRNA
/ Multivariate analysis
/ Nuclear Proteins - genetics
/ Nuclear Proteins - metabolism
/ Nuclear Proteins - physiology
/ Nucleoli
/ Oncology
/ Phenotypes
/ Predictive Value of Tests
/ Prognosis
/ Proteins
/ Pseudouridine synthase
/ Risk factors
/ Survival Analysis
/ Tumor Cells, Cultured
/ Tumors
2020
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The nucleolar-related protein Dyskerin pseudouridine synthase 1 (DKC1) predicts poor prognosis in breast cancer
by
Hyder, Ayman
, Abou-Dobara, Mohamed I.
, Rakha, Emad A.
, El-Gammal, Hekmat L.
, Green, Andrew R.
, Dalton, Leslie W.
, Aleskandarany, Mohammed A.
, Mohammed, Omar J.
, Elsharawy, Khloud A.
in
631/67/1347
/ 692/4028
/ Adult
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Biomarkers, Tumor - physiology
/ Biomedical and Life Sciences
/ Biomedicine
/ Breast cancer
/ Breast Neoplasms - diagnosis
/ Breast Neoplasms - genetics
/ Breast Neoplasms - mortality
/ Breast Neoplasms - therapy
/ Cancer Research
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cell Cycle Proteins - physiology
/ Cohort Studies
/ Datasets as Topic
/ Drug Resistance
/ Epidemiology
/ Female
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Genotypes
/ Humans
/ Hypertrophy
/ Immunohistochemistry
/ Information theory
/ Medical prognosis
/ Middle Aged
/ Molecular Medicine
/ mRNA
/ Multivariate analysis
/ Nuclear Proteins - genetics
/ Nuclear Proteins - metabolism
/ Nuclear Proteins - physiology
/ Nucleoli
/ Oncology
/ Phenotypes
/ Predictive Value of Tests
/ Prognosis
/ Proteins
/ Pseudouridine synthase
/ Risk factors
/ Survival Analysis
/ Tumor Cells, Cultured
/ Tumors
2020
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The nucleolar-related protein Dyskerin pseudouridine synthase 1 (DKC1) predicts poor prognosis in breast cancer
by
Hyder, Ayman
, Abou-Dobara, Mohamed I.
, Rakha, Emad A.
, El-Gammal, Hekmat L.
, Green, Andrew R.
, Dalton, Leslie W.
, Aleskandarany, Mohammed A.
, Mohammed, Omar J.
, Elsharawy, Khloud A.
in
631/67/1347
/ 692/4028
/ Adult
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Biomarkers, Tumor - physiology
/ Biomedical and Life Sciences
/ Biomedicine
/ Breast cancer
/ Breast Neoplasms - diagnosis
/ Breast Neoplasms - genetics
/ Breast Neoplasms - mortality
/ Breast Neoplasms - therapy
/ Cancer Research
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cell Cycle Proteins - physiology
/ Cohort Studies
/ Datasets as Topic
/ Drug Resistance
/ Epidemiology
/ Female
/ Gene expression
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Genotypes
/ Humans
/ Hypertrophy
/ Immunohistochemistry
/ Information theory
/ Medical prognosis
/ Middle Aged
/ Molecular Medicine
/ mRNA
/ Multivariate analysis
/ Nuclear Proteins - genetics
/ Nuclear Proteins - metabolism
/ Nuclear Proteins - physiology
/ Nucleoli
/ Oncology
/ Phenotypes
/ Predictive Value of Tests
/ Prognosis
/ Proteins
/ Pseudouridine synthase
/ Risk factors
/ Survival Analysis
/ Tumor Cells, Cultured
/ Tumors
2020
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The nucleolar-related protein Dyskerin pseudouridine synthase 1 (DKC1) predicts poor prognosis in breast cancer
Journal Article
The nucleolar-related protein Dyskerin pseudouridine synthase 1 (DKC1) predicts poor prognosis in breast cancer
2020
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Overview
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
< 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,
DKC1
mRNA 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 692/4028
/ Adult
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Biomarkers, Tumor - physiology
/ Biomedical and Life Sciences
/ Breast Neoplasms - diagnosis
/ Breast Neoplasms - mortality
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cell Cycle Proteins - physiology
/ Female
/ Gene Expression Regulation, Neoplastic
/ Genomes
/ Humans
/ mRNA
/ Nuclear Proteins - metabolism
/ Nuclear Proteins - physiology
/ Nucleoli
/ Oncology
/ Proteins
/ Tumors
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