Impact pathway and gene ontology analyses of FOXC2 ‐correlated genes in melanoma reveal a role for the FOXC2 transcription factor in several oncogenic pathways and processes

Background The forkhead box family transcription factor FOXC2 has emerged as an important oncogene in cancers of epithelial origin, where it has been associated with several hallmarks of cancer progression. In this study, we provide clinical evidence of a role for FOXC2 in the progression of melanoma. Using bioinformatics‐based approaches, we aimed to gain insight into the oncogenic functions of this transcription factor in this cancer of non‐epithelial origin. Methods We investigated multiple RNA‐sequencing datasets from biopsies of independent melanoma patient cohorts to identify genes whose expression correlated with that of the FOXC2 gene. These data were analysed using topology‐based Impact Pathway and high‐specificity pruning Gene Ontology approaches. Results We identified novel biologic pathways and processes significantly impacted by FOXC2 ‐correlated genes, including those related to Rap1 signalling and collagen fibril organisation. For these novel pathways/processes, as well as others previously linked with the activity of FOXC2, our study also revealed specific FOXC2 ‐correlated genes associated with these biological phenomena. Conclusions Together, our data offer novel insights into the oncogenic functions of FOXC2 in melanoma and other cancers.