Survival is associated with repressive histone trimethylation markers in both HR-positive HER2-negative and triple-negative breast cancer patients.

About 30% of patients with hormone receptor (HR)-positive breast cancers and up to 50% of human epidermal growth factor receptor 2 (HER2)-positive patients develop progression due to treatment resistance, highlighting the need for more differentiated tumor classifications within the breast cancer molecular subtype to optimize the therapies. We aim to examine the roles of histone modification markers. The levels of common repressive histone markers, histone H3 lysine 9 trimethylation (H3K9me3), histone H3 lysine 27 trimethylation (H3K27me3), and histone H4 lysine 20 trimethylation (H4K20me3), in tumors were evaluated by immunohistochemistry for 914 breast cancer patients. The subjects were followed up until December 2021. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. For H3K27me3, patients with the high level had a longer PFS rate (81.3%) than that with the low level (73.9%) within HR-positive/HER2-negative subtype during a follow-up of 85 months only in univariate analysis (P < 0.05). For H3K9me3, the significant association between the high level of it and the longer OS [HR = 0.57, P < 0.05] was found within HR-positive/HER2-negative subtype in multivariate analysis. For H4K20me3, patients with the high level had a longer both OS [HR = 0.38] and PFS [HR = 0.46] within HR-positive/HER2-negative subtype, while had a shorter OS [HR = 3.28] in triple-negative breast cancer (TNBC) in multivariate analysis (all P < 0.05). H3K9me3 and H3K27me3 were the potential prognostic markers for breast cancer patients with HR-positive/HER2-negative subtype. Importantly, H4K20me3 was a robust prognostic marker for both HR-positive/HER2-negative and TNBC patients.

Association of Enolase-1 with Prognosis and Immune Infiltration in Breast Cancer by Clinical Stage.

Purpose: Enolase-1 (ENO1) plays a key role in malignancies. Previous studies on the association between ENO1 expression and breast cancer prognosis had yielded inconsistent results. In the present study, we assessed the prognostic effect of ENO1 in breast cancer using Guangzhou Breast Cancer Study (GZBCS) cohort with full consideration of the potential confounders and the modification effects. The results were further validated in the TCGA-BRCA cohort and explained by tumor immunity. Methods: ENO1 protein expressions were evaluated by immunohistochemistry in tissue microarrays from 961 patients with primary invasive breast cancer. Chi-square tests were used to assess the association of ENO1 levels with the patient's characteristics. Cox regression models were applied to assess the prognostic effects. The TCGA-BRCA cohort was utilized to validate the results and explore the potential mechanisms. The immune infiltration was determined using the CIBERSORT and ssGSEA algorithms; the correlation between ENO1 expression and the abundance of tumor-infiltrating immune cells (TIICs) and scores of immune-related functions was evaluated by Wilcoxon signed-rank tests and Spearman's rank test. Results: ENO1 protein expression exerted a protective effect on OS in stage I/II patients (HR=0.58, 95% CI: 0.35-0.96) but not in stage III patients (HR=1.42, 95% CI: 0.81-2.49, P interaction=0.04) in GZBCS; consistent results were obtained at mRNA levels in TCGA cohort. Immune infiltration analyses revealed that ENO1 was positively correlated with multiple antitumor TIICs (including M1 macrophages, B cells, CD8 T cells, T helper 2 cells, and NK cells) only in stage I/II but not stage III patients. Conclusion: A higher expression of ENO1 was associated with a better prognosis only in early-stage breast cancer, which may be related to the different effects of ENO1 on immune infiltration, suggesting that ENO1 may be a promising target for precision immunotherapy in breast cancer.

The Circ_CARM1 controls cell migration by regulating CTNNBIP1 in anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide-transformed 16HBE cells.

BACKGROUND: Circular RNAs (circRNAs) have an important role in the development and progression of human tumors, including lung cancer. Yet, their role in lung cancer induced by benzo(a)pyrene (B[a]P) remains unclear. In this study, circRNA chips and qRT-PCR were used to examine downregulated circRNAs in malignantly transformed 16HBE cells (16HBE-T) induced by B[a]P. Five down-regulated circRNAs were found, among which hsa_circ_0004552 (circ_CARM1) had the most significant downregulation. Consequently, the role of circ_CARM1 on 16HBE-T cells biological behavior was further examined using several in vitro experiments. MATERIALS AND METHODS: Detecting RNA expression via qRT-PCR. Fluorescence in situ hybridization (FISH) was used to identify the localization of circ_CARM1 in 16HBE-T. The effect of circ_CARM1 on cell behavior (cell migration, proliferation, and apoptosis) was explored by transfecting cells with a vector carrying an overexpression and then using wound healing, transwell migration assay, and flow cytometry. Also, the regulation mechanism for circ_CARM1, miR-1288-3p, and CTNNBIP1 was studied by Dual-Luciferase® Reporter (DLR™) Assay System and western blotting. RESULTS: Reduced expression of circ_CARM1 is observed in 16HBE-T. The overexpression of circ_CARM1 further inhibited the migration of 16HBE-T cells but did not affect cell proliferation and apoptosis. Furthermore, bioinformatic analysis and Dual-Luciferase® Reporter (DLR™) Assay System showed that the competitive binding of circ_CARM1 and miR-1288-3p enhanced the expression of CTNNBIP1, thereby inhibiting the migration of 16HBE-T cells. CONCLUSION: Downregulation of circ_CARM1 can stimulate the expression of miR-1288-3p, thereby reducing the expression of CTNNBIP1, spurring cell migration.

Accuracy Evaluation of Circular RNA in Diagnosing Lung Cancer in a Chinese Population.

Circular RNA (circRNA) is a class of recently discovered noncoding RNA. circRNAs can be used as a potent noninvasive biological marker of cancer owing to their varying expression levels among different cancers. This meta-analysis was performed to assess the accuracy of circRNAs in diagnosing lung cancer. A total of eight studies identified through searching the PubMed, Web of Science, Cochrane Library, and Embase from inception to March 20, 2019 were eligible for this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratio were 0.77 (95% confidence interval (CI): 0.73-0.80; I 2 = 8.98%), 0.76 (95% CI: 0.69-0.82; I 2 = 63.12%), 3.17 (95% CI: 2.43-4.14; I 2 = 33.18%), 0.31 (95% CI: 0.26-0.37; I 2 = 20.36%), and 10.26 (95% CI: 6.87-15.31; I 2 = 97.18%), respectively. The area under the receiver operating characteristic curve was 0.78 (95% CI: 0.74-0.81). The study confirmed the use of circRNAs in diagnosing lung cancer in a Chinese population.