Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Unidad Asociada IIBB-CSIC, 08003 Barcelona, Spain.
Medical Oncology Department, Hospital Duran i Reynals, Catalan Institute of Oncology, L'Hospitalet, 08908 Barcelona, Spain.
Cells. 2023 Mar 8;12(6):843. doi: 10.3390/cells12060843.
Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The β-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.
胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，预后极差。不幸的是，尽管免疫检查点抑制剂在许多实体肿瘤中最近取得了革命性进展，但这些药物在 GBM 患者的总生存期中并未显示出获益。因此，需要新的潜在治疗靶点以及诊断、预后和/或预测生物标志物，以改善该人群的结局。β-半乳糖苷结合蛋白半乳糖凝集素-1（Gal-1）是一种具有广泛促肿瘤功能的蛋白质，如增殖、侵袭、血管生成和免疫抑制。在这里，我们通过免疫组化在均质治疗的 GBM 队列（GLIOCAT 项目）中评估了 Gal-1 的表达，并将其表达与临床和分子数据相关联。我们观察到 Gal-1 是 GBM 的一个负预后因素。有趣的是，我们观察到在间充质/经典亚型中 Gal-1 的表达水平高于侵袭性较低的原神经亚型。我们还观察到 Gal-1 的表达与 CD4 T 细胞和巨噬细胞的免疫抑制特征以及几个 GBM 既定的生物标志物（包括 SHC1、PD-L1、PAX2、MEOX2、YKL-40、TCIRG1、YWHAG、OLIG2、SOX2、Ki-67 和 SOX11）相关。此外，Gal-1 水平在具有更好预后的 4 级突变星形细胞瘤中显著降低。我们的结果证实了 Gal-1 作为预后因素的作用，并提示其作为 GBM 免疫抑制生物标志物的价值。
