Malignant glioma is the most common solid tumor of the adult brain, with high lethality and poor prognosis. Hence, identifying novel and reliable biomarkers can be advantageous for diagnosing and treating glioma. Several galectins encoded by LGALS genes have recently been reported to participate in the development and progression of various tumors; however, their detailed role in glioma progression remains unclear. Herein, we analyzed the expression and survival curves of all LGALS across 2,217 patients with glioma using The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Rembrandt databases. By performing multivariate Cox analysis, we built a survival model containing LGALS1, LGALS3, LGALS3BP, LGALS8, and LGALS9 using TCGA database. The prognostic power of this panel was assessed using CGGA and Rembrandt datasets. ESTIMATE and CIBERSORT algorithms confirmed that patients in high-risk groups exhibited significant stromal and immune cell infiltration, immunosuppression, mesenchymal subtype, and isocitrate dehydrogenase 1 (IDH1) wild type. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), CancerSEA, and Gene Set Enrichment Analysis (GSEA) showed that pathways related to hypoxia, epithelial-to-mesenchymal transition (EMT), stemness, and inflammation were enriched in the high-risk group. To further elucidate the function of LGALS in glioma, we performed immunohistochemical staining of tissue microarrays (TMAs), Western blotting, and cell viability, sphere formation, and limiting dilution assays following lentiviral short hairpin RNA (shRNA)-mediated LGALS knockdown. We observed that LGALS expression was upregulated in gliomas at both protein and mRNA levels. LGALS could promote the stemness maintenance of glioma stem cells (GSCs) and positively correlate with M2-tumor-associated macrophages (TAMs) infiltration. In conclusion, we established a reliable survival model for patients with glioma based on LGALS expression and revealed the essential roles of LGALS genes in tumor growth, immunosuppression, stemness maintenance, pro-neural to mesenchymal transition, and hypoxia in glioma.

Glioblastoma (GBM) is the most malignant type of glioma with the worst prognosis. Traditional therapies (surgery combined with radiotherapy and chemotherapy) have limited therapeutic effects. As a novel therapy emerging in recent years, immunotherapy is increasingly used in glioblastoma (GBM), so we expect to discover more effective immune targets. FGL2, a member of the thrombospondin family, plays an essential role in regulating the activity of immune cells and tumor cells in GBM. Elucidating the role of FGL2 in GBM can help improve immunotherapy efficacy and design treatment protocols. This review discusses the immunosuppressive role of FGL2 in the GBM tumor microenvironment and its ability to promote malignant tumor progression while considering FGL2-targeted therapeutic strategies. Also, we summarize the molecular mechanisms of FGL2 expression on various immune cell types and discuss the possibility of FGL2 and its related mechanisms as new GBM immunotherapy.