Pan-Cancer Analysis of the N6-Methyladenosine Eraser FTO as a Potential Prognostic and Immunological Biomarker

Background: Fat mass and obesity-associated protein (FTO) is a critical N6methyladenosine (m6A) demethylase that participates in tumorigenesis and is associated with the prognosis of patients in some cancers. However, the key roles of FTO in pan-cancer are still largely obscure. Methods: FTO expression levels in pan-cancer were estimated via the Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and The Cancer Genome Atlas (TCGA) databases. Univariate survival analysis was used to estimate the effects of FTO on prognosis. In addition, we used the Tumor Immune Evaluation Resource (TIMER) to assess the immune cell infiltration of FTO gene across cancers. The association of FTO expression with immune checkpoint genes expression, DNA mismatch repair (MMR) gene mutation, DNA methyltransferases, microsatellite instability (MSI), and tumor mutational burden (TMB) was investigated using Spearman's correlation analysis. Moreover, Gene Set Enrichment Analysis (GSEA) was utilized to identify critical pathways in cancers. The STRING website was used to reveal the protein-protein interaction (PPI) network of FTO. Results: FTO was aberrantly expressed across cancers and survival analysis demonstrated that its expression was associated with clinical prognosis of many cancer patients. Specifically, FTO expression was significantly associated with immune infiltrating cells in colon adenocarcinoma, kidney renal clear cell carcinoma, and liver hepatocellular carcinoma. In addition, FTO expression was significantly associated with immune checkpoint genes expression, MMR, DNA methyltransferases levels, TMB, and MSI in multiple cancers. Moreover, the GSEA unveiled that FTO was involved in the regulation of tumors and immune-related signaling pathways. In addition, several m6A related genes were implicated in the PPI network of FTO. Conclusion: FTO was related to patients' prognosis and tumor immune infiltrates in various cancers, and may serve as a novel and potential prognostic and immune biomarker in human pan-cancer.