Impact of DAXX and ATRX expression on telomere length and prognosis of breast cancer patients.


Journal

Journal of the Egyptian National Cancer Institute
ISSN: 2589-0409
Titre abrégé: J Egypt Natl Canc Inst
Pays: England
ID NLM: 9424566

Informations de publication

Date de publication:
28 Aug 2020
Historique:
received: 01 05 2020
accepted: 16 07 2020
entrez: 29 8 2020
pubmed: 29 8 2020
medline: 11 8 2021
Statut: epublish

Résumé

Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. The loss of death domain-associated protein (DAXX) and α-thalassemia/mental retardation X-linked protein (ATRX) plays a role in telomere lengthening and stability. This study aims to evaluate the prognostic significance of telomere length (TL) and its association with DAXX and ATRX proteins in breast cancer (BC). Our study used the FISH technique to detect peptide nucleic acid (PNA) in the peripheral blood cells of a cohort of BC patients (n = 220) and a control group of apparently healthy individuals (n = 100). Expression of DAXX and ATRX proteins was evaluated using immunohistochemistry (IHC) in all BC tissues. Patients with a shorter TL had worse disease-free survival (DFS) and overall survival (OS). There were significant associations between shorter TL and advanced disease stages, lymph node metastasis, and positive HER2/neu expression. DAXX protein expression was significantly correlated with TL. Lower DAXX expression was significantly with shorter DFS. Assessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.

Sections du résumé

BACKGROUND BACKGROUND
Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. The loss of death domain-associated protein (DAXX) and α-thalassemia/mental retardation X-linked protein (ATRX) plays a role in telomere lengthening and stability. This study aims to evaluate the prognostic significance of telomere length (TL) and its association with DAXX and ATRX proteins in breast cancer (BC). Our study used the FISH technique to detect peptide nucleic acid (PNA) in the peripheral blood cells of a cohort of BC patients (n = 220) and a control group of apparently healthy individuals (n = 100). Expression of DAXX and ATRX proteins was evaluated using immunohistochemistry (IHC) in all BC tissues.
RESULTS RESULTS
Patients with a shorter TL had worse disease-free survival (DFS) and overall survival (OS). There were significant associations between shorter TL and advanced disease stages, lymph node metastasis, and positive HER2/neu expression. DAXX protein expression was significantly correlated with TL. Lower DAXX expression was significantly with shorter DFS.
CONCLUSION CONCLUSIONS
Assessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.

Identifiants

pubmed: 32856116
doi: 10.1186/s43046-020-00045-1
pii: 10.1186/s43046-020-00045-1
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Co-Repressor Proteins 0
DAXX protein, human 0
Molecular Chaperones 0
Nuclear Proteins 0
ATRX protein, human EC 3.6.4.12
X-linked Nuclear Protein EC 3.6.4.12

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

34

Auteurs

Marwa T Hussien (MT)

Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

Shimaa Shaban (S)

Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

Doaa F Temerik (DF)

Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt. Doaaftemerik@gmail.com.

Shaaban R Helal (SR)

Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Eman Mosad (E)

Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

Sahar Elgammal (S)

Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Abeer Mostafa (A)

Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

Eman Hassan (E)

Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

Abeer Ibrahim (A)

Department of Medical Oncology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

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Classifications MeSH