Pan-cancer associations of FBL expression with clinical outcomes, genomic features, and the tumor immune microenvironment

Fibrillarin (FBL) is a nucleolar 2′-O-methyltransferase required for rRNA modification and ribosome biogenesis. Although FBL has been implicated in tumorigenesis, its pan-cancer expression pattern, prognostic relevance, immune associations and potential biological functions remain incompletely defined. We performed an integrated pan-cancer analysis of FBL across 33 tumor types using public multi-omics and clinical datasets. FBL was significantly upregulated in multiple cancers and was associated with advanced tumor stage and unfavorable prognosis. Genomic analyses showed recurrent copy number amplification of FBL, which was linked to poorer clinical outcomes. FBL expression was also correlated with multiple indicators of genomic instability, including tumor mutational burden, microsatellite instability, homologous recombination deficiency, neoantigen load, ploidy and tumor purity. Immune-related analyses further indicated that FBL was negatively associated with antitumor immune cell infiltration and was related to cancer stemness, promoter methylation and m1A, m5C and m6A RNA modification regulators. Functional enrichment analyses suggested that FBL-associated genes were mainly involved in ribosome biogenesis, translation and spliceosome pathways. This pan-cancer study suggests that FBL expression is associated with ribosome biogenesis-related pathways, genomic instability-related features, and tumor microenvironment characteristics across human cancers. FBL may represent a molecular feature associated with clinical outcomes, genomic characteristics, tumor immune microenvironment patterns, and RNA modification-related signatures across human cancers. Further experimental studies are required to determine whether FBL directly contributes to these processes.