Association of HDAC8 Expression with Pathological Findings in Triple Negative and Non-Triple Negative Breast Cancer: Implications for Diagnosis

Abstract

Background: Previous data have shown the tumorigenicity roles of HDAC8 in breast cancer. More recently, the oncogenic effects of this molecule have been revealed in TNBC. The present study aimed to determine the diagnostic value of HDAC8 for the differentiation of TNBC from nTNBC tumors. Methods: A total of 50 cancerous and normal adjacent tumor specimens were obtained, and the clinical and pathological findings of studied subjects were recorded. The expression of HDAC8 gene was determined by qRT-PCR. Also, immunohistochemical staining was performed on tissue samples. Results: Our results showed that the expression of HDAC8 in breast cancer tissues was significantly higher than the normal adjacent tissues (p = 0.0011). HDAC8 expression was also observed to be higher in TNBC patients than nTNBC group (p = 0.0013). In addition, in the TNBC group, there was a significant association between the HDAC8 overexpression and tumor characteristics, including tumor size (p = 0.039), lymphatic invasion (p = 0.01), tumor grade (p = 0.02), and perineural invasion (p < 0.05). The cutoff value was fixed at 0.6279 r.u., and the corresponding sensitivity and specificity were found to be 73.91% and 70.37%, respectively. Conclusion: According to the findings, among the other markers, HDAC8 oncogene may be used as a potential tumor marker in diagnosis of TNBC tumors.

Small molecule agents for triple negative breast cancer: Current status and future prospects

“…In TNBC preclinical models, both HDAC6 inhibitors YSL-109 and 10 g have exhibited significant anti-proliferative activity [ 225 , 226 ]. The overexpression of HDAC8 in TNBC is associated with TNBC tumor size, lymphatic infiltration, and tumor grade [206] . HDAC8 can activate YY1 or Hippo/YAP signaling to promote the proliferation and migration of TNBC [ 227 , 228 ].…”

“…The dynamic equilibrium between HDAC and histone acetylase (HAT) intricately governs chromosome modification and gene expression. Perturbations in this balance, characterized by heightened histone deacetylation and diminished acetylation, can induce aberrations in the cell cycle, thereby fostering tumorigenesis [206] . Studies have shown that histone differences are associated with TNBC [206] .…”

“…Perturbations in this balance, characterized by heightened histone deacetylation and diminished acetylation, can induce aberrations in the cell cycle, thereby fostering tumorigenesis [206] . Studies have shown that histone differences are associated with TNBC [206] . HDAC inhibitors may play a role in TNBC by inhibiting HDAC activity, decreasing the level of histone deacetylation, regulating glycolytic metabolism [207] , inhibiting angiogenesis and tumor growth [ 208 , 209 ], and inducing tumor autophagy and apoptosis [210] .…”

Epigenetic Regulations of Perineural Invasion in Head and Neck Squamous Cell Carcinoma

“…HDAC8 was found to be overexpressed in OSCC tissues, and HDAC8 silencing significantly inhibited the proliferation of OSCC cells by the induction of apoptosis through caspases activation and pro-survival autophagy ( Ahn and Yoon, 2017 ). In breast cancer tissue, there was a significant association between HDAC8 overexpression and perineural invasion ( p < 0.05) ( Menbari et al, 2020 ).…”

Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis

“…HDAC8 was demonstrated to form complex with SMAD3/4 and transcriptionally suppresses SIRT7 thereby reduce metastasis and increase chemotherapy efficacy in breast cancer (Tang et al, 2020). Meanwhile, the expression of HDAC8 is related to the pathological results in triple-negative breast cancer (TNBC), which indicated the potential in the diagnosis of TNBC tumors (Menbari et al, 2020). HDAC class III sirtuins are found to be overexpressed in breast cancer.…”