HDAC2 overexpression is a poor prognostic factor of breast cancer patients with increased multidrug resistance-associated protein expression who received anthracyclines therapy

Abstract

Objective: Previous studies have revealed the association of multidrug resistance with histone deacetylases inhibitors treatment in cancer cells. But little data were available for the correlation of histone deacetylases and drug-resistant-related proteins in breast cancer tissue. This study aimed to exploring the association of histone deacetylases expression with clinicopathological features, drugresistant-related proteins, prognosis and therapeutic responses in breast cancer patients. Methods: We performed immunohistochemistry to study the expression of HDAC1 and HDAC2 in 226 breast cancer and 34 breast fibroadenoma patients, and the expression of breast cancer resistance protein, P-glycoprotein, lung resistance protein and multidrug resistance protein in 226 breast cancer. Results: In breast cancer, HDAC2 expression was significantly increased than in fibroadenoma (P = 0.015), and correlated with lymph node metastasis (P = 0.002), advanced clinical stages (P = 0.016) and high histological grade (P = 0.001). Significant positive correlations were found between HDAC2 and Ki67, HDAC1 and multidrug resistance protein, HDAC2 and breast cancer resistance protein, HDAC2 and multidrug resistance protein. HDAC2 positive expression was associated with shorter overall survival (P = 0.035) of breast cancer patients. In addition, HDAC2-positive expression was significantly associated with shorter overall survival in multidrug resistance protein-positive patients (P = 0.034), but not in multidrug resistance protein-negative patients (P = 0.530). HDAC2-positive expression was associated with shorter survival in patients who received chemotherapy containing anthracyclines (overall survival, P = 0.041; disease-free survival, P = 0.084), but not in patients who received chemotherapy without anthracyclines (overall survival, P = 0.679; disease-free survival, P = 0.708). Conclusions: HDAC2 overexpression correlated with the metastasis, progression and the increased Ki67, multidrug resistance protein expression in breast cancer, and HDAC2 could be a prognostic factor of breast cancer patients, especially the patients who received anthracyclines therapy.

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

“…LINC01234 acts as a ceRNA to modulate CBFB expression in gastric cancer by absorbing miR-204-5p [33]. Herein, we uncovered a ceRNA mechanism of ARAP1-AS1-miR-2110-HDAC2 in BC cells, among which miR-2110 has been identified as an onco-suppressor in in neuroblastoma [34] and HDAC2 is a well-recognized transcriptional co-repressor that plays a carcinogenic role in BC progression [35][36][37]. In our research, miR-2110 overexpression inhibited cell proliferation, migration and stimulated cell apoptosis in BC.…”

HDAC2 and PCNA expression is correlated to decreasing of endoxifen sensitivity in human breast cancer stem cells ALDH+

“…Other study reported that HDAC2 overexpression correlated with the metastasis, progression and the increased Ki67, multidrug resistance protein expression in breast cancer. 17 HDAC2 will remove acetyl groups from histones and creates a closed chromatin structure that prevents the transcription of genes involved in growth arrest, differentiation, and apoptosis. 11 The expression of PCNA is correlated with high cytological grading and poor prognosis in renal carcinoma.…”

The landscape of DNA methylation-mediated regulation of long non-coding RNAs in breast cancer

“…The genes were ranked by the frequency of enrichments in biological process. Of the top 10 genes in HMLncs, nine were demonstrated to be associated with BRCA: FOXJ1 [ 31 ], HDAC2 [ 32 ], WNT1 [ 33 ], SOX18 [ 34 ], NOTCH4 [ 35 ], SP3 [ 36 ], HOXA11 [ 37 ], HOXC11 [ 38 ] and FOXD3 [ 39 ]. In addition, there were six genes coding transcription factors in the top 10 genes ( FOXJ1 , SOX18 , SP3 , HOXA11 , HOXC11 and FOXD3 ) (Figure 3E ).…”