Bioinformatic analysis of the prognostic value and potential regulatory network of FOXF1 in papillary thyroid cancer

FOXF1 belongs to the forkhead family of transcription factors. In this study, we aimed to explore the expression profile of FOXF1 in papillary thyroid cancer (PTC) and corresponding adjacent normal tissues, by using data from The Cancer Genome Atlas-Thyroid Cancer (TCGA-THCA) and The Genotype-Tissue Expression (GTEx) project. Also, we studied its prognostic significance in PTC and its potential regulatory network. Results showed that FOXF1 expression was significantly lower in PTC tissues compared with adjacent normal tissues. Subgroup analysis only confirmed the downregulation in classical histological variant, but not in tall-cell and follicular variants. FOXF1 downregulation was associated with advanced T stages, positive nodal invasion, and advanced pathological stages of the classical variants. FOXF1 expression might be a fair prognostic marker in terms of recurrence, which independently predicted favorable RFS (HR:0.114, 95%CI: 0.045-0.289, p < .001). We examined FOXF1 somatic mutations, gene-level copy number alterations (CNAs) and the methylation status of 57 CpG sites in more than 350 classical PTC cases. However, no expression-related genetic and epigenetic alterations were identified. Based on 20,048 genes with RNA-seq data, we identified 16 genes that showed strongly positive co-expression (Pearson's r = 0.6) with FOXF1. Available evidence showed that some of the genes have well-characterized tumor suppressive effects. We hypothesized that some of these genes might be the upstream regulators or downstream effectors of FOXF1 in classical PTC. In conclusion, FOXF1 mRNA was typically downregulated in classical PTC. Its expression might be a specific and independent prognostic biomarker in terms of RFS in classical PTC patients.