Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m 6A-dependent miR-17-5p maturation-induced ZBTB4 depletion.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and its mechanisms of occurrence and development remain unclear. In this study, we aim to investigate the role and molecular mechanisms of the demethylase FTO (fat mass and obesity-associated protein) in TNBC. Through analysis of public databases, we identify that FTO may regulate the maturation of miR-17-5p and subsequently influence the expression of zinc finger and BTB domain-containing protein 4 (ZBTB4), thereby affecting the occurrence and progression of TNBC. We screen for relevant miRNAs and mRNAs from the GEO and TCGA databases and find that the FTO gene may play a crucial role in TNBC. In vitro cell experiments demonstrate that overexpression of FTO can suppress the proliferation, migration, and invasion ability of TNBC cells and can regulate the maturation of miR-17-5p through an m 6A-dependent mechanism. Furthermore, we establish a xenograft nude mouse model and collect clinical samples to further confirm the role and impact of the FTO/miR-17-5p/ZBTB4 regulatory axis in TNBC. Our findings unveil the potential role of FTO and its underlying molecular mechanisms in TNBC, providing new perspectives and strategies for the research and treatment of TNBC.

Prognostic significance of platelet-to-lymphocyte ratio (PLR) in patients with breast cancer treated with neoadjuvant chemotherapy: a meta-analysis.

OBJECTIVE: Platelet-to-lymphocyte ratio (PLR), known as a key systemic inflammatory parameter, has been proved to be associated with response to neoadjuvant therapy in breast cancer (BC); however, the results remain controversial. This meta-analysis was carried out to evaluate the prognostic values of PLR in patients with BC treated with neoadjuvant chemotherapy (NACT). DESIGN: Meta-analysis. DATA SOURCES: Relevant literature published on the following databases: PubMed, Embase, Web of Science databases and the Cochrane Library. ELIGIBILITY CRITERIA: All studies involving patients with BC treated with NACT and peripheral blood pretreatment PLR recorded were included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted and evaluated HR/OR and its 95% CI of survival outcomes, pathological complete response (pCR) rate and clinicopathological parameters. RESULTS: The last search was updated to 31 December 2022. A total of 22 studies with 5533 patients with BC treated with NACT were enrolled in the final meta-analysis. Our results demonstrate that elevated PLR value appears to correlate with low pCR rate (HR 0.77, 95% CI 0.67 to 0.88, p<0.001, I2=75.80%, Ph<0.001) and poor prognosis, including overall survival (OS) (HR 1.90, 95% CI 1.39 to 2.59, p<0.001; I2=7.40%, Ph=0.365) and disease-free survival (HR 1.97, 95% CI 1.56 to 2.50, p<0.001; I2=0.0%, Ph=0.460). Furthermore, PLR level was associated with age (OR 0.86, 95% CI 0.79 to 0.93, p<0.001, I2=40.60%, Ph=0.096), menopausal status (OR 0.83, 95% CI 0.76 to 0.90, p<0.001, I2=50.80%, Ph=0.087) and T stage (OR 1.05, 95% CI 1.00 to 1.11, p=0.035; I2=70.30%, Ph=0.005) of patients with BC. CONCLUSIONS: This meta-analysis demonstrated that high PLR was significantly related to the low pCR rate, poor OS and disease-free survival (DFS) of patients with BC treated with NACT. Therefore, PLR can be used as a potential predictor biomarker for the efficacy of NACT in BC.

The efficacy and safety of nivolumab in the treatment of advanced melanoma: a meta-analysis of clinical trials.

BACKGROUND: Nivolumab has become a therapeutic regimen for the treatment of patients with advanced melanoma. The goal of this study was to assess the efficacy and safety of nivolumab in patients with advanced melanoma. METHODS: A systematic search from January 2008 to August 2015 with "nivolumab" and "advanced melanoma" as search terms was performed for possible clinical trials. According to the hazard ratio and the 95% confidence interval (CI) for progression-free survival (PFS), rates of objective response, complete response, partial response, rates of toxic effects, and the efficacy and safety of nivolumab were assessed. Using the software Review Manager (version 5.3) a meta-analysis was performed. RESULTS: There were four trials with 1,910 patients included. Based on the four trials, the pooled hazard ratio of PFS was 0.53 (95% CI, 0.43-0.66; P<0.001). The pooled risk ratio for the objective response rate, complete response, and partial response was 2.98% (95% CI, 2.38%-3.73%; P<0.001), 3.71% (95% CI, 2.67%-5.14%; P<0.001), and 2.51% (95% CI, 2.12%-2.99%; P<0.001), respectively. Nivolumab plus ipilimumab therapy significantly increased the risk of grade 3/4 rash and fatigue. CONCLUSION: Nivolumab-based therapy prolonged PFS in treatment of advanced melanoma, with less adverse effects. Nivolumab appears to be a favorable treatment option as a novel, targeted anticancer agent, for patients with advanced melanoma.