Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

Abstract

Background: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.Methods: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. We also showed that knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases. Results: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, we identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC. Conclusion: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.

Screening and prognostic value of potential biomarkers for ovarian cancer

“…Depletion of FBXO16 results in increased levels of β-catenin, which in turn promotes cancer cell invasion, tumor growth and epithelial-mesenchymal transition (21). In breast cancer, FBXO16 is considered to be a potential clinical target and prognostic biomarker for patients with different molecular types of breast cancer (22). In addition, it has been reported that increasing the number of cytotoxic Tim-3 + /CD8 + T cells can promote effective anti-tumor immunity, and PTPN2 is an attractive tumor immunotherapy target in immune cells (23).…”

Identification of SNPs and Candidate Genes for Milk Produce Ability in Yorkshire Pig

“…SLC5A12 was an active source of lactate transmembrane transporter, which is mainly involved in sodium ion transport [50,51]. FBXO2 ,and MAD2L2 were involved in ubiquitination processes [52,53], which regulated the milk protein and fat metabolic mechanism [54]. DRAXIN was related to Akt, which could impact milk synthesis [55,56].…”