Identification of integrative molecular and clinical profiles of Fibrinogen-like protein 2 in gliomas using 1323 samples

Background: Fibrinogen-like protein 2 (FGL2), a member of the fibrinogen superfamily, has been described to augment immunosuppression in gliomas. However, the precise clinical molecular features and the prognostic relevance of FGL2 in gliomas remain unclear. Therefore, a comprehensive analysis of the role of FGL2 in gliomas would provide insights into the therapeutic implications for this disease. Methods: Totally, 1323 glioma samples with RNA-seq and microarray data from TCGA and CGGA databases were used to clarify the clinical significance and molecular profile of FGL2 in glioma. The findings were further validated through immunohistochemistry (IHC). Results: The transcriptional level of FGL2 was positively associated with tumor grade in gliomas, which was confirmed at the protein level through IHC staining. Consistently, FGL2 was significantly enriched in isocitrate dehydrogenase wild-type tumors and the mesenchymal subtype of gliomas. We also demonstrated FGL2 expression correlated with high immune scores and infiltration of immune cell populations, including T cells, macrophages and B cells. Pearson's correlation analysis revealed that FGL2-related genes correlated with inflammatory-immune responses, particularly T cell-mediated immune response. Additionally, FGL2 expression was found tightly associated with immune checkpoints PD-L1 and PD-L2. Clinically, patients with high FGL2 expression exhibited unfavorable overall survival. Conclusion: Our results provide the integrative molecular and clinical profiles of FGL2 in gliomas and emphasize the importance of prospective studies on the FGL2-related immune-inflammatory network.