NRF2 is an important regulatory transcription factor involved in tumor immunity and tumorigenesis. In this study, we firstly identified that FKBP4/NR3C1 axis was a novel negative regulator of NRF2 in human breast cancer (BC) cells. The effect of FKBP4 appeared to be at protein level of NRF2 since it could not suppress the expression of NRF2 at mRNA level. Bioinformatics analysis and in vitro experiments further demonstrated that FKBP4 regulated NRF2 via regulating nuclear translocation of NR3C1. We then reported that naringenin, a flavonoid, widely distributed in citrus and tomato, could suppress autophagy and proliferation of BC cells through FKBP4/NR3C1/NRF2 signaling pathway in vitro and in vivo. Naringenin was also found to promote dendritic cell (DC) differentiation and maturation through FKBP4/NR3C1/NRF2 axis. Therefore, our study found that naringenin could induce inhibition of autophagy and cell proliferation in BC cells and enhance DC differentiation and maturation, at least in part, though regulation of FKBP4/NR3C1/NRF2 signaling pathway. Identification of FKBP4/NR3C1/NRF2 axis would provide insights for novel anti-tumor strategy against BC among tumor microenvironment.

Purpose: FKBP4 is a member of the immunophilin protein family, which plays a role in immunoregulation and basic cellular processes involving protein folding and trafficking associated with HSP90. However, the relationship between abnormal expression of FKBP4 and clinical outcome in luminal A subtype breast cancer (LABC) patients remains to be elucidated.

Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. In current study, 11 DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. Four hundred and eighty two predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top 20 lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients' overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. Three hundred and twenty target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the topest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients' OS.

Mastoscopic axillary lymph node dissection (MALND) is a currently used and safe surgical treatment option for breast cancer. However, the extensive application of MALND is still debatable because of the use of conventional axillary lymph node dissection (CALND). Therefore, in the current study, we aimed to compare the efficacy and safety of MALND and CALND for obtaining evidence-based conclusions about the short-term and long-term outcomes of MALND for patients with breast cancer. PubMed, Web of Science, Cochrane Library, and CNKI were comprehensively searched for articles published between January 1998 and January 2019. Then Newcastle-Ottawa scale was used for quality assessment. The Review Manager software version 5.0 was utilized for generating forest maps and funnel plots. Twelve studies including 2157 patients were selected for the meta-analysis. There were no significant differences in the number of lymph node dissections, tumor recurrence rate, axillary drainage, postoperative hospitalization time, and tumor size between the MALND and CALND groups (P > .05). In the MALND group, the surgery time was longer, while the incidence of intraoperative bleeding was lesser and the duration of drainage was shorter than those in the CALND group (P < .01). The complications in the MALND group were also fewer than those in the CALND group (P < .05). The results of the current study showed that MALND is reliable and feasible for breast cancer owing to the lesser incidence of intraoperative bleeding, shorter drainage duration, and lower incidence of complications compared to CALND.

Objective: To investigate the relationship between FKBP prolyl isomerase 5 ( FKBP5) gene expression and CD8 T cells in tumour progression and immunology of the luminal B subtype of breast cancer (LBBC) using bioinformatics analyses. Methods: The Gene Expression Profiling Interactive Analysis 2, Human Protein Atlas and breast cancer gene-expression miner v4.5 databases were used for data mining and analysing FKBP5, its co-expressed genes and CD8 T cell-related markers. The Tumor IMmune Estimation Resource 2.0 database was used for analysing the correlation and prognosis of FKBP5 and CD8 T cell infiltration level in LBBC. Results: Upregulated FKBP5 expression was correlated with improved survival in LBBC. Upregulated FKBP5-related CD8 T cell markers were also demonstrated to be significantly correlated with better survival in LBBC and might play a role in the biological activity of FKBP5. Conclusion: These findings suggest that FKBP5 and its associated CD8 T cell infiltration are potential benign prognostic indicators for LBBC.