Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker FAM111A in Diffuse Lower-Grade Glioma

BACKGROUND: Family with sequence similarity 111 member A (FAM111A), as a replication factor required for proliferating cell nuclear antigen (PCNA) loading, has been demonstrated a possible association with carcinogenesis. However, the role of FAM111A in lower-grade glioma (LGG) remains unclear. We aim at investigating the expression and function of FAM111A in lower-grade glioma at the molecular and clinical levels. METHODS: In total, 711 lower-grade glioma samples were analyzed in our research, including 182 RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) dataset and 529 RNA-seq data from The cancer Genome Atlas (TCGA) dataset. R language and the GraphPad software were used for the majority of statistical analysis and graphical work. RESULTS: FAM111A expression was overexpressed in WHO grade III and IDH-wildtype lower-grade glioma. FAM111A was significantly downregulated in the IDHmut-Codel molecular subtype. Univariate and multivariate Cox analysis demonstrated that FAM111A was an independent prognostic factor in LGG patients. Functional characterization of FAM111A revealed that it was associated with inflammatory response and immune response to tumor cells. FAM111A could also act as an indicator of the stromal and immune population, especially for monocytic lineage, myeloid dendritic cells and fibroblasts. It was positively correlated with macrophages, especially the M2 macrophage cells. Furthermore, FAM111A revealed predictive value for the immune subtypes and immune checkpoint blockade therapy. CONCLUSION: FAM111A expression was closely related to the malignant phenotype, molecular pathology and immune response of lower-grade glioma. It might be a promising target for LGG immunotherapeutic strategies.