Clinicopathological significance and underlying molecular mechanism of downregulation of basonuclin 1 expression in ovarian carcinoma.

In this study, we aim to identify the clinical significance of basonuclin 1 (BNC1) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of -2.339 (95% CI: -3.649 to -1.028, P < 0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI: 0.445-0.989, P < 0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low-BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1, friend leukemia virus integration 1 (FLI1) may be a potential upstream TF of BNC1. Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

Autologous haematopoietic stem cell transplantation restores the suppressive capacity of regulatory B cells in systemic sclerosis patients.

OBJECTIVES: The rationale of autologous haematopoietic stem cell transplantation (AHSCT) for autoimmune diseases is that high-dose immunosuppression eradicates autoreactive T and B cells and the infused autologous haematopoietic stem cells promote reconstitution of a naïve and self-tolerant immune system. The aim of this study was to evaluate the reconstitution of different B cell subsets, both quantitatively and functionally, in SSc patients treated with AHSCT. METHODS: Peripheral blood was harvested from 22 SSc patients before transplantation and at 30, 60, 120, 180 and 360 days post-AHSCT. Immunophenotyping of B cell subsets, B cell cytokine production, signalling pathways and suppressive capacity of regulatory B cells (Bregs) were assessed by flow cytometry. RESULTS: Naïve B cell frequencies increased from 60 to 360 days post-AHSCT compared with pre-transplantation. Conversely, memory B cell frequencies decreased during the same period. Plasma cell frequencies transiently decreased at 60 days post-AHSCT. IL-10-producing Bregs CD19+CD24hiCD38hi and CD19+CD24hiCD27+ frequencies increased at 180 days. Moreover, the phosphorylation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase increased in B cells reconstituted post-AHSCT. Notably, CD19+CD24hiCD38hi Bregs recovered their ability to suppress production of Th1 cytokines by CD4+ T cells at 360 days post-AHSCT. Finally, IL-6 and TGF-ß1-producing B cells decreased following AHSCT. CONCLUSION: Taken together, these results suggest improvements in immunoregulatory and anti-fibrotic mechanisms after AHSCT for SSc, which may contribute to re-establishment of self-tolerance and clinical remission.