Prognostic values of F-box members in breast cancer: an online database analysis and literature review

Abstract

Introduction: F-box proteins are the substrate-recognizing subunits of SKP1 (S-phase kinase-associated protein 1)-cullin1-F-box protein (SCF) E3 ligase complexes that play pivotal roles in multiple cellular processes, including cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. Dysregulation of F-box proteins may lead to an unbalanced proteolysis of numerous protein substrates, contributing to progression of human malignancies. However, the prognostic values of F-box members, especially at mRNA levels, in breast cancer (BC) are elusive. Methods: An online database, which is constructed based on the gene expression data and survival information downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/), was used to investigate the prognostic values of 15 members of F-box mRNA expression in BC. Results: We found that higher mRNA expression levels of FBXO1, FBXO31, SKP2, and FBXO5 were significantly associated with worse prognosis for BC patients. While FBXO4 and β-TrCP1 were found to be correlated to better overall survival (OS). Conclusion: The associated results provide new insights into F-box members in the development and progression of BC. Further researches to explore the F-box protein-targetting reagents for treating BC are needed.

Keywords: F-box; breast cancer; literature review; prognostic value.

Figure 1. The prognostic values of the mRNA expression of F-box in all BCs

Overexpression of FBXO1 (A), FBXO31 (B), SKP2 (C), and FBXO5 (D) are significantly associated with worse OS in all BC patients. Overexpression of FBXO4 (E) and β-TrCP1 (F) are associated with better prognosis.

Figure 2. The prognostic values of the mRNA expression of F-box in luminal A type BCs

The high expression of FBXO1 (A), SKP2 (B), and FBXO5 (C) are correlated to worse survival, and FBXW8 (D) and β-TrCP1 (E) are associated with longer OS in luminal A type BC patients.

Figure 3. The prognostic values of some selected F-box in luminal B type, HER2-expressing or Basal-like BCs

Survival curves of FBXO4 (A) are plotted for luminal B type BC patients. Survival curves of FBXW8 (B) and FBXL3 (C) are plotted for HER2-overexpressing BC patients. Survival curves of FBXW8 (D) are plotted for basal-like BC patients.