Bioinformatics analysis of the clinicopathological and prognostic significance of BAG3 mRNA in gynecological cancers

J Obstet Gynaecol. 2023 Dec;43(2):2228899. doi: 10.1080/01443615.2023.2228899.

Abstract

BAG3 is a co-chaperone BAG family protein that plays important roles in protein homeostasis, cell survival, cell motility, and tumour metastasis. This study aimed to clarify the clinicopathological and prognostic implications of BAG3 mRNA expression in tumours. We performed bioinformatics analysis on BAG3 mRNA expression using TCGA, XIANTAO, UALCAN, and Kaplan-Meier plotter databases. BAG3 mRNA expression was downregulated in breast and endometrial cancers and positively correlated with favourable PAM50 subtyping in breast cancer,clinical stage and short overall survival in ovarian cancer and negatively correlated with T stage, clinical stage, and histological grade in cervical and endometrial cancers. The top BAG3-related pathways included ligand-receptor interactions and activity, DNA packaging and nucleosomes, hormonal responses, membrane regions, microdomains and rafts, and endosomes in breast cancer; ligand-receptor interactions, transmembrane transporters and channels, cell adhesion, and keratinisation in cervical cancer; ligand-receptor interactions, anion transmembrane transporters, lipoproteins, keratinisation, cell adhesion, and protein processing in endometrial cancer; metabolism of porphyrin, chlorophyll, pentose, uronic acid, ascorbate, and alternate and cell adhesion in ovarian cancer. BAG3 expression could represent a potential marker for carcinogenesis, histogenesis, aggressive behaviours, and prognosis in gynecological cancers.IMPACT STATEMENTWhat is already known on this subject? BAG3 regulates cell activity, autophagy, and resistance to apoptosis through multiple domains and plays an important role in tumour development. BAG3 positively regulates tumour cell invasion and migration in cervical and ovarian cancers.What do the results of this study add? BAG3 expression is closely associated with histogenesis, clinicopathology, and prognosis in gynecological cancers and is involved in signalling pathways associated with the control of cell proliferation, migration, invasion, and drug resistance in tumours.What are the implications of these findings for clinical practice and/or further research? Abnormal BAG3 expression can be employed as a possible marker of tumour development, invasion, and prognosis, providing new ideas for treating cancer.

Keywords: BAG3; aggressive behaviour; bioinformatics analysis; carcinogenesis; gynecological cancers; prognosis.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Apoptosis Regulatory Proteins
  • Breast Neoplasms* / genetics
  • Cell Line, Tumor
  • Computational Biology
  • Endometrial Neoplasms*
  • Female
  • Humans
  • Ligands
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Prognosis
  • RNA, Messenger

Substances

  • Adaptor Proteins, Signal Transducing
  • RNA, Messenger
  • Ligands
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human