Department of Neurosurgery, Cancer Center, Zhejiang Provincial People's Hospital Affiliated to Hangzhou Medical College, Hangzhou, China.
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Endocrinol (Lausanne). 2022 Aug 3;13:943300. doi: 10.3389/fendo.2022.943300. eCollection 2022.
The IGFBP family of insulin-like growth factor binding proteins has important biological functions in the organism. However, the role of the IGFBP family in low-grade glioma (LGG) has not been fully explored.
We validated the clinical value of the IGFBP family using RNA-seq and clinical data of LGG in the TCGA and constructed an IGFBPScore using LASSO-regression analysis for prognosis prediction, subtype determination, and treatment sensitivity determination. Subsequently, we explored the role of the IGFBP family in the development of LGG using PanCanAtlas data.
Our results suggest that most IGFBP family members were aberrantly expressed and were strongly associated with poor prognosis in LGG. By constructing an IGFBPScore representing the IGFBP family, we found that tumor samples with a high IGFBPScore had a glioblastoma-like mutation pattern characterized by IDH1wt, EGFRmut, PTENmut, and NF1mut with hypo-methylation and glioma stem cell (GSC) diversity. In contrast, the low IGFBPScore group was characterized by IDH1mut accompanied by TP53mut, CICmut, and ATRXmut, and had hyper-methylation status as well as the GSC restriction. Additionally, the high-IGFBPScore group had a high inflammation phenotype with increased immune antigenicity and increased infiltration of immune molecules and cells, as well as a high extracellular matrix phenotype and enhanced multiple metabolic pathways compared with the immune-quiet phenotype of the low-IGFBPScore group, which was strongly associated with poor prognosis.
Our study provides a summary analysis and a theoretical basis for the biological role and clinical value of the IGFBP family in LGG, providing an important therapeutic target for LGG.
胰岛素样生长因子结合蛋白家族（IGFBPs）在机体中具有重要的生物学功能。然而，IGFBPs 家族在低级别胶质瘤（LGG）中的作用尚未被充分探索。
我们使用 RNA-seq 和 TCGA 中 LGG 的临床数据验证了 IGFBP 家族的临床价值，并使用 LASSO 回归分析构建了 IGFBPScore 来进行预后预测、亚型确定和治疗敏感性确定。随后，我们使用 PanCanAtlas 数据探讨了 IGFBP 家族在 LGG 发展中的作用。
我们的结果表明，大多数 IGFBP 家族成员在 LGG 中表达异常，与预后不良密切相关。通过构建代表 IGFBP 家族的 IGFBPScore，我们发现具有高 IGFBPScore 的肿瘤样本具有胶质母细胞瘤样的突变模式，其特征为 IDH1wt、EGFRmut、PTENmut 和 NF1mut，伴有低甲基化和胶质瘤干细胞（GSC）多样性。相比之下，低 IGFBPScore 组的特征为 IDH1mut 伴有 TP53mut、CICmut 和 ATRXmut，并且具有高甲基化状态以及 GSC 限制。此外，高 IGFBPScore 组具有高炎症表型，增加了免疫原性，增加了免疫分子和细胞的浸润，以及高细胞外基质表型和增强的多种代谢途径，与低 IGFBPScore 组的免疫安静表型相比，具有预后不良的强烈相关性。
我们的研究为 IGFBP 家族在 LGG 中的生物学作用和临床价值提供了总结分析和理论依据，为 LGG 提供了一个重要的治疗靶点。
