Pan-cancer analysis identifies FAM111B as a biomarker for immune suppression microenvironment in low-grade gliomas

Mutations in the family with sequence similarity 111 member B (FAM111B) are responsible for POIKTMP, a rare hereditary disease characterized by poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis. Previous studies have primarily focused on the roles of FAM111B in genomic instability and cellular homeostasis, whereas its pan-cancer expression patterns, mechanistic roles, and immune-related relevance, particularly its functions in glioma, have not been systematically investigated. Therefore, this study aimed to systematically investigate the biological and immune-related roles of FAM111B in the development and progression of lower-grade glioma (LGG), and to assess its potential as a prognostic biomarker and therapeutic target.

We analyzed the expression profile of FAM111B across pan-cancer datasets using publicly available databases and assessed its prognostic significance. We investigated the associations between FAM111B expression and tumor mutational burden (TMB), microsatellite instability (MSI), pyroptosis, ferroptosis, and the overall gene mutation landscape. Focusing on glioma, we validated the differential expression of FAM111B among LGG subtypes using patient tumor tissue specimens and glioma cell lines in vitro. Additionally, we conducted protein-protein interaction (PPI) network analysis and functional enrichment analysis. Subsequently, we examined the correlations between FAM111B expression and tumor immune cell infiltration, inflammatory activity, and immune checkpoint expression. Finally, the tumor-promoting role of FAM111B in glioma was further validated through in vitro experiments and intracranial xenograft models established using luciferase-expressing LN229 cells in male BALB/c nude mice, with tumor growth monitored by bioluminescence imaging.

FAM111B exhibited differential expression across pan-cancer datasets and was significantly associated with patient prognosis. FAM111B expression showed notable correlations with tumor genomic instability and cell death-related molecular features. We further demonstrated that FAM111B was differentially expressed among LGG subtypes and identified FAM111B as an independent prognostic factor for LGG. Subsequent investigations revealed significant associations between FAM111B expression and tumor immune cell infiltration, inflammatory activity, and immune checkpoint expression. Functionally, in vitro experiments demonstrated that FAM111B enhanced glioma cell proliferation, invasion, and migration, and in vivo studies further demonstrated that FAM111B promoted glioma progression by fostering an immunosuppressive tumor microenvironment.

Our research indicates that FAM111B is a reliable immune-associated marker of poor prognosis in glioma.