Pan-Cancer Analysis Identifies YTHDF2 as an Immunological and Prognostic Biomarker

Abstract Background N6-methyladenosine (m6A) modification is a dynamic and reversible post-transcriptional RNA modification prevalent in eukaryotic cells. As a member of m6A reader protein, YT521-B homology domain family 2 (YTHDF2) has been demonstrated involving in many vital biological process, whereas its role in cancers remains unclear. Methods We evaluated the immunohistochemical staining of tissue sections from 51 hepatocellular carcinoma patients and TIMER database to investigate the association between the YTHDF2 expression and the infiltration of immunocytes. TCGA, GEPIA2, GEO and GTEx databases were used to analyze the differential expression of YTHDF2 in various cancers. R 3.6.3 is used for Data visualization. Results YTHDF2 is overexpressed in most tumors, and the increased YTHDF2 expression is associated with poor OS, PFI, and DSS. YTHDF2 expression is also positively correlated with MMR, TMB and MSI. Moreover, GSEA revealed that functions associated with cell adhesion, cell cycle and immune regulation were enriched in YTHDF2 overexpression tumors. Further study verified the participation of YTHDF2 in immune regulation through its correlation with ICP genes and the infiltration of immunocytes in tumor microenvironment. Notably, we demonstrated a positive correlation between YTHDF2 expression and the infiltration of CD8+ T cells and macrophages, as well as exhausted T lymphocytes. Conclusion YTHDF2 can be used as a new therapeutic target and a potential biomarker for cancer immune evasion and poor prognosis.