ArticleDiscover oncology2025
Integrated mendelian randomization and bioinformatics approach unveiling the immunological and prognostic significance of FBXO2 in breast cancer.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBreast cancer (BRCA) is a typical females' malignant tumors. Ubiquitin-proteasome system (UPS) is a critical pathway for pathogenesis of BRCA. Activation of UPS is determined by SKP1-cullin 1-F-box protein (SCF) E3 ligase complexes. F-Box Protein 2 (FBXO2), a pivotal member of F-box proteins family, is associated with UPS. FBXO2 has attracted increasing attention in various cancers, yet its relationship with many cancer types is still unclear. Therefore, systematic research on FBXO2 and pan-cancer is very important for understanding BRCA progression and drug resistance.
methodTranscriptome expression data of 33 cancer types were acquired from the Cancer Genome Atlas (TCGA) database. Wilcoxon test was performed to estimate the molecular characteristic of FBOX2 across human pan-cancer analyses. To confirmed the relationship between FBXO2 and BRCA, mendelian randomization (MR) was conducted. Kaplan-Meier (KM) analyses was used to evaluated the survival features of FBXO2. Additionally, protein and methylation level of FBXO2 were examined using Wilcoxon test. Single-cell sequence analysis was further applied to confirm the importance of FBXO2. The underlying mechanism of FBXO2 was explored from various perspectives, including gene function, immune checkpoint and tumor microenvironment. Finally, stable FBXO2-knockdown and overexpression models in MDA-MB-231 and MCF-7 were established, and functional assays including CCK-8, Transwell, and wound healing experiments were conducted to validate the role of FBXO2 in vitro.
resultOur pan-cancer analysis revealed that FBXO2 was up-regulated in multiple cancer types, but was significantly down-regulated in BRCA. MR analysis confirmed a caused relationship between reduced FBXO2 expression and increased BRCA risk. Consistent with transcriptional findings, FBXO2 protein levels were also decreased in BRCA. KM analysis indicated that low FXBO2 expression was associated with poor overall survival (OS) and recurrence free survival (RFS) in BRCA patients. Single-cell sequence analysis further revealed that FBXO2 obviously enriched in malignant epithelial cells. In vitro functional experiments demonstrated that knockdown of FBXO2 significantly promoted cell proliferation, migration and invasion, whereas its overexpression suppressed these malignant phenotypes in BRCA.
conclusionIn conclusion, our comprehensive analysis revealed that FBXO2 plays a critical tumor-suppression role in BRCA, with its down-regulation contributing to poor prognosis. Furthermore, FBXO2 was implicated in immune regulation and tumor microenvironment remodeling. Our findings provided novel insights into the pathogenesis of BRCA.
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