FUCA2 Is a Prognostic Biomarker and Correlated With an Immunosuppressive Microenvironment in Pan-Cancer.

ABSTRACT

Background: The expression of Fucosidase, alpha-L-2 (FUCA2) varies across tumors. However, its role in various tumor types and relationship with the tumor immune microenvironment (TIME) is poorly defined. Methods: We analyzed profiles of FUCA2 expression using datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Next, gene alteration, clinical characteristics and prognostic values of FUCA2 were elucidated based on TCGA pan-cancer data. This was followed by gene set enrichment analysis by R software. Relationships between FUCA2 expression and immune infiltration and immune-related genes were also evaluated. Moreover, the association of immune cell infiltration with FUCA2 expression was evaluated across three different sources of immune cell infiltration data, namely the TIMER online, ImmuCellAI databases, as well as a published study. In addition, MTT assays was also conducted to validate the oncogene role of FUCA2 in lung cancer cells. Results: FUCA2 was upregulated in most tumors, and this was significantly associated with poor survival rates. Gene set enrichment analysis uncovered that FUCA2 correlated with immune pathways in different tumor types. FUCA2 expression was positively related to tumor associated macrophages (TAMs), especially M2-like TAMs. Moreover, FUCA2 level showed a positive relationship with most immunosuppression genes, including programmed death-ligand 1 (PD-L1), transforming growth factor beta 1 (TGFB1), and interleukin-10 (IL10) in most cancer types. FUCA2 knockdown inhibited the cell viability in lung cancer cells. Conclusions: Our study reveals that FUCA2 is a potential oncogene and is indicative biomarker of a worse prognosis in pan-cancer. High FUCA2 expression may contribute to increased infiltration of TAMs and associates with an immunosuppressive microenvironment, providing a potential target for tumor therapy.