FGL2 As a Predictive Biomarker for Prognosis and Immunotherapy in Bladder Cancer

Background: Metastasis and immunosuppression result in unfavorable prognosis in bladder cancer (BLCA). FGL1 and FGL2 are two members of the fibrinogen-related proteins family, but their potential effects on BLCA remain elusive. Methods: The expression profile of FGL1 and FGL2 in BLCA was analyzed in multiple databases. Furthermore, the expression of FGL2 was validated in BLCA tissues. The predictive capability of FGL2 was evaluated by Kaplan-Meier analysis, univariate analysis, and multivariate Cox regression. A nomogram model was constructed based on FGL2 expression and clinicopathological parameters for clinical practice. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analyses (GSEA) were performed to investigate enrichment in the biological processes. In addition, the correlation between FGL2 and immunological characteristics in the BLCA tumor microenvironment (TME), including tumor-infiltrating immune cells (TICs), cancer-immunity cycles, immune checkpoint molecules (ICPs), immunophenoscores (IPS), and response to anti-PD-L1 immunotherapy was further analyzed. Results: FGL2 was found to be downregulated in BLCA due to hypermethylation of the FGL2 promoter region, which was associated with an unfavorable prognosis. Moreover, BLCA patients with high FGL2 expression exhibited better response to immunotherapy. Conclusions: Our research revealed that FGL2 was downregulated in BLCA and was negatively correlated with DNA methylation. High FGL2 expression was confirmed as an independent risk for prognosis. Moreover, FGL2 is a promising indicator for the response to immunotherapy in patients with BLCA.