Pan‐cancer analyses reveal multi‐omic signatures and clinical implementations of the forkhead‐box gene family

Abstract

BackgroundForkhead box (FOX) proteins belong to one of the largest transcription factor families and play crucial roles in the initiation and progression of cancer. Prior research has linked several FOX genes, such as FOXA1 and FOXM1, to the crucial process of carcinogenesis. However, the overall picture of FOX gene family across human cancers is far from clear.MethodsTo investigate the broad molecular signatures of the FOX gene family, we conducted study on multi‐omics data (including genomics, epigenomics and transcriptomics) from over 11,000 patients with 33 different types of human cancers.ResultsPan‐cancer analysis reveals that FOX gene mutations were found in 17.4% of tumor patients with a substantial cancer type‐dependent pattern. Additionally, high expression heterogeneity of FOX genes across cancer types was discovered, which can be partially attributed to the genomic or epigenomic alteration. Co‐expression network analysis reveals that FOX genes may exert functions by regulating the expression of both their own and target genes. For a clinical standpoint, we provided 103 FOX gene‐drug target‐drug predictions and found FOX gene expression have potential survival predictive value. All of the results have been included in the FOX2Cancer database, which is freely accessible at http://hainmu‐biobigdata.com/FOX2Cancer.ConclusionOur findings may provide a better understanding of roles FOX genes played in the development of tumors, and help to offer new avenues for uncovering tumorigenesis and unprecedented therapeutic targets.

FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration

“…The forkhead box (FOX) proteins constitute a family of transcription factors characterized by their well-preserved fork-head and winged-helix DNA binding domains, which display a specific affinity for the universally conserved DNA sequence 5ʹ-TTGTTTAC-3ʹ ( 20 , 21 , 22 ). FOXK, comprising FOXK1 and FOXK2, harbor a forkhead-associated (FHA) domain rich in phospho-threonine-residues that distinguishes it from other FOX transcription factors ( 23 ).…”