Prognostic Significance and Immunological Role of FBXO5 in Human Cancers: A Systematic Pan-Cancer Analysis

Abstract

F-box protein 5 (FBXO5), an essential subunit of the ubiquitin protein ligase complex, is increasingly recognized to exhibit important biological effects in regulating tumor occurrence and progression. The present research was intended to systematically investigate the latent roles of FBXO5 in prognosis and immunological function across cancers. Pan-cancer analyses of FBXO5 were performed based upon publicly available online databases, mainly including the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UCSC Xena, cBioPortal, and ImmuCellAI, revealing the possible relationships between FBXO5 and prognosis, DNA methylation, tumor microenvironment (TME), infiltration of immune cells, immune-related genes, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI). The results suggested that FBXO5 was expressed at a high level in numerous tumor cell lines with significant upregulation in most cancers as opposed to normal tissues. Of note, elevated expression of FBXO5 was significantly related to an unfavorable prognosis in many cancer types. Furthermore, DNA methylation and TME were confirmed to display evident correlation with the expression of FBXO5 in several malignancies. Moreover, FBXO5 expression was remarkably positively correlated with the levels of infiltrating Treg cells and Tcm cells in most tumors, but negatively correlated with tumor-infiltrating CD8+ T cells, NK/NKT cells, and Th2 cells. Meanwhile, FBXO5 was demonstrated to be co-expressed with the genes encoding immune activating and suppressive factors, chemokines, chemokine receptors, and major histocompatibility complex (MHC). Immune checkpoints, TMB, and MSI were also overtly associated with FBXO5 dysregulation among diverse kinds of cancers. Additionally, the enrichment analyses showed close relationships between FBXO5 expression and the processes related to cell cycle and immune inflammatory response. These findings provided a detailed comprehension of the oncogenic function of FBXO5. Because of its crucial roles in cancer immunity and tumorigenesis, FBXO5 may serve as a novel prognostic indicator and immunotherapeutic target for various malignancies.