Regulators of histone acetylation are promising epigenetic targets for therapy in breast cancer. In this study, we comprehensively analyzed the expression of histone acetylation modulator genes in breast cancer using TCGA data sources. A gene signature composed of eight histone acetylation modulators (HAMs) was found to be effective for the classification and prognosis of breast cancers, especially in the HER2-enriched and basal-like molecular subtypes. The eight genes consist of two histone acetylation writers (GTF3C4 and CLOCK), two erasers (HDAC2 and SIRT7) and four readers (BRD4, BRD7, SP100, and BRWD3). Both histone acetylation writer genes and eraser genes were found to be differentially expressed between the two groups indicating a close relationship exists between overall histone acetylation level and prognosis of breast cancer in HER2-enriched and basal-like breast cancer.

Background/Objectives: The purpose of this study was to investigate the association between HER-2 expression and clinicopathological characteristics, biochemical recurrence (BCR) rate, and BCR-free survival in localized prostate cancer (PCa) patients after radical prostatectomy (RP). Methods: Between January 2018 and December 2019, 44 patients with pathologically confirmed localized PCa who underwent RP were included in this study. According to the expressed level of HER-2 protein, patients were divided into four cohorts: cohort-1 (HER-2 0), cohort-2 (HER-2 1+ or 2+), cohort-3 (HER-2 0 or 1+), and cohort-4 (HER-2 2+); the clinicopathological and clinical outcomes were analyzed and compared between cohort-1 and cohort-2, and cohort-3 and cohort-4, respectively. Univariable and multivariable COX regression models and Kaplan–Meier curves were used to determine the association between HER-2 expression and clinicopathological outcomes, including Gleason score (GS), pathological T (pT) stage, positive surgical margins (PSM), and BCR-free survival, respectively. Results: The median follow-up time was 43 months (IQR 35–49). Among the 44 patients, 20 (45.5%) exhibited HER-2 immuno-reactivity, including 14 (31.8%) with HER-2 1+, 6 (13.64%) with HER-2 2+, and 0 (0%) with HER-2 3+ staining. The proportion of patients with PSM was significantly lower in the HER-2 0 group than in those with HER-2 1+ or 2+ (25.0% vs. 65.0%, p = 0.008). Multivariable logistics regression models revealed that HER-2 1+ or 2+ was an independent risk factor that was strongly associated with a higher proportion of PSM (OR, 2.69; 95% CI, 0.62–11.71, p = 0.042). A total of 18 (40.9%) patients experienced BCR after surgery, including 6 (25%) in cohort-1 and 12 (60.0%) in cohort-2 (p = 0.019), as well as 13 (34.2%) in cohort-3 and 5 (83.3%) in cohort-4 (p = 0.023). Kaplan–Meier analysis showed that patients in cohort-1 (HER-2 0) had significantly longer BCR-free survival than those in cohort-2 (HER-2 1+ or 2+) (p < 0.001), and those in cohort-3 had longer BCR-free survival than those in cohort-4 (p < 0.001). Furthermore, patients with PSM showed significantly shorter BCR-free survival compared to those with patients with negative surgical margins (NSM) (p = 0.005). Multivariable Cox regression analysis revealed that HER-2 1+, 2+ (HR, 17.00; 95% CI, 1.38–210.22, p < 0.001), HER-2 2+ (HR, 2.85; 95% CI, 1.23–3.25, p = 0.004), and PSM (HR, 6.12; 95% CI, 3.08–11.72, p = 0.007) were all significant independent predictors of BCR following surgery. Conclusions: HER-2 expression is a common phenomenon in PCa; nearly half of the proportion of localized PCa had HER-2 1+ or 2+, but the cases that expressed HER-2 3+ were rare. Cases with HER-2 1+ or 2+ were more likely to develop BCR compared with HER-2 0. The HER-2 1+ or 2+ expression was closely associated with a higher incidence of PSM and was an independent predictor of shorter BCR-free survival in patients with localized prostate cancer after radical prostatectomy.