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

Exp Biol Med (Maywood). 2022 Jan;247(2):106-119. doi: 10.1177/15353702211052036. Epub 2021 Oct 13.

Abstract

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.

Keywords: Basonuclin 1; ovarian carcinoma; prognosis; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / immunology*
  • Down-Regulation / immunology*
  • Female
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Memory B Cells / immunology*
  • Memory B Cells / pathology
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Transcription Factors / immunology*
  • Tumor Suppressor Proteins / immunology*

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • BNC1 protein, human