RESUMO
BACKGROUND: Several recent studies suggest that chromodomain-helicase -DNA-binding domains (CHDs) are linked with cancers. We explored the association between chromodomain-Helicase-DNA-binding domain proteins and breast cancer (BrCa) and introduced potential prognostic markers using various databases. MATERIALS AND METHODS: We analyzed the expression of the CHD family and their prognostic value in BrCa by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. The association of CHD expression and immune infiltrating abundance was studied via the TIMER database. In addition, microRNAs related to the CHD family were identified by using the MirTarBase online database. RESULTS: The present study indicated that compared to normal tissues, BrCa tissues showed increased mRNA levels of CHD3/4/7 but decreased CHD2/5/9 expression. Interestingly, We also found a positive correlation between CHD gene expression and the infiltration of macrophage, neutrophil, and dendritic cells in BrCa, except CHD3/5. The Kaplan-Meier Plotter analysis suggested that high expression levels of CHD1/2/3/4/6/8/9 were significantly related to shorter relapse-free survival (RFS), while higher mRNA expression of CHD1, CHD2, CHD8, and CHD9 was significantly associated with longer overall survival of BrCa patients. The miRNAs of hsa-miR-615-3p and hsa-let-7b-5p were identified as being more correlated with the CHD family. CONCLUSION: The altered expression of some CHD members was significantly related to clinical cancer outcomes, and CHD1/2/8/9 could serve as potential prognostic biomarkers to improve the survival of BrCa patients. However, to evaluate the studied CHD members in detail are needed further investigations including experimental validation.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/genética , DNA Helicases/genética , DNA Helicases/metabolismo , Taxa de Sobrevida , Regulação Neoplásica da Expressão GênicaRESUMO
Chromatin is highly dynamic, undergoing continuous global changes in its structure and type of histone and DNA modifications governed by processes such as transcription, repair, replication, and recombination. Members of the chromodomain helicase DNA-binding (CHD) family of enzymes are ATP-dependent chromatin remodelers that are intimately involved in the regulation of chromatin dynamics, altering nucleosomal structure and DNA accessibility. Genetic studies in yeast, fruit flies, zebrafish, and mice underscore essential roles of CHD enzymes in regulating cellular fate and identity, as well as proper embryonic development. With the advent of next-generation sequencing, evidence is emerging that these enzymes are subjected to frequent DNA copy number alterations or mutations and show aberrant expression in malignancies and other human diseases. As such, they might prove to be valuable biomarkers or targets for therapeutic intervention.
