Abstract
BackgroundTelomere 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.ResultsPatients 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.ConclusionAssessing 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.
Highlights
Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis
Either ATRX or Death domain-associated protein (DAXX) protein inhibition was observed to be strongly correlated with alternative lengthening of telomeres (ALT) in neuroblastomas, pancreatic neuroendocrine tumors, and sarcomas indicating that the inhibition of these proteins plays vital roles in the initiation of the ALT phenotype [8]
Telomere length in breast cancer (BC) patients and control group The mean telomere length (TL) was longer in the BC group compared with the control group (P = 0.001)
Summary
Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. Telomere length (TL) conservation has been reported to play a key role in continuing everlasting replication and tumorigenesis in cancer cells. It is considered a hallmark of cancer in which transforming cells achieve eternality by upregulating. Li et al [11] found that ATRX and DAXX have no direct function as ALT suppressors Instead, they revealed that their loss persuades a delayed onset of telomere replication stress that activates the ALT-associated DNA repair pathway while simultaneously compromising mutant cell growth. They revealed that their loss persuades a delayed onset of telomere replication stress that activates the ALT-associated DNA repair pathway while simultaneously compromising mutant cell growth They proved that this action is distinct from TL and pre-existing endogenous telomerase activity
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