Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou, China.
Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer Med. 2023 Feb;12(4):4951-4967. doi: 10.1002/cam4.5187. Epub 2022 Aug 31.
A subgroup of glioma carry genetic 4q12 amplification including platelet derived growth factor receptor α (PDGFRA) and insulin like growth factor binding protein 7 (IGFBP7). However, the prognosis of PDGFRA and IGFBP7 in glioma is unclear.
The prognosis of PDGFRA and IGFBP7 was determined using cox regression and Kaplan-Meier survival analysis. Pathways associated with IGFBP7 were analyzed through gene set enrichment analysis (GSEA). Immune profiling of glioma was determined using "ESTIMATE" and "TIMER" database.
PDGFRA amplification or expression was not correlated with the outcomes of glioblastoma (GBM). IGFBP7 but not PDGFRA was over-expressed in GBM. IGFBP7 over-expression was correlated with the unfavorable outcomes of GBM. In lower grade glioma (LGG), PDGFRA over-expression was not correlated with the unfavorable prognosis of LGG, while, IGFBP7 was a prognostic biomarker of LGG. LGG patients with IGFBP7 lower expressions had prolonged clinical overall survival. Combination of IDH mutation, LGG grade and IGFBP7 achieved even better prognostic effects in LGG. Moreover, IGFBP7 was over-expressed in glioma patients with wild type IDH or with high grades. IGFBP7 over-expression was correlated with the unfavorable outcomes of glioma. Furthermore, IGFBP7 was hypo-methylated in GBM or LGG patients without IDH mutations. IGFBP7 hyper-methylation was correlated with the lower overall survival of GBM or LGG. LGG patients with wild type IDH and with IGFBP7 hypo-methylation demonstrated even worse prognosis. IGFBP7 was associated with multiple immune-related signaling pathways in GBM or LGG. The stromal score, immune score and the infiltrations of immune cells were also correlated with IGFBP7 and the prognosis of LGG.
IGFBP7 but not PDGFRA served an ideal prognostic marker and therapeutic target of glioma.
胶质母细胞瘤（GBM）中有一个亚组携带包括血小板衍生生长因子受体α（PDGFRA）和胰岛素样生长因子结合蛋白 7（IGFBP7）在内的 4q12 扩增。然而，PDGFRA 和 IGFBP7 在胶质母细胞瘤中的预后尚不清楚。
采用 COX 回归和 Kaplan-Meier 生存分析确定 PDGFRA 和 IGFBP7 的预后。通过基因集富集分析（GSEA）分析与 IGFBP7 相关的途径。利用“ESTIMATE”和“TIMER”数据库对胶质母细胞瘤进行免疫分析。
PDGFRA 扩增或表达与胶质母细胞瘤（GBM）的结果无关。IGFBP7 而不是 PDGFRA 在 GBM 中过度表达。IGFBP7 过表达与 GBM 的不良预后相关。在低级别胶质瘤（LGG）中，PDGFRA 过表达与 LGG 的不良预后无关，而 IGFBP7 是 LGG 的预后标志物。IGFBP7 低表达的 LGG 患者临床总生存期延长。在 LGG 中，联合 IDH 突变、LGG 分级和 IGFBP7 可获得更好的预后效果。此外，IGFBP7 在野生型 IDH 或高级别胶质瘤患者中过度表达。IGFBP7 过表达与胶质瘤的不良预后相关。此外，在无 IDH 突变的 GBM 或 LGG 患者中 IGFBP7 呈低甲基化。IGFBP7 高甲基化与 GBM 或 LGG 的总生存率降低相关。IDH 野生型和 IGFBP7 低甲基化的 LGG 患者预后更差。IGFBP7 与 GBM 或 LGG 中的多个免疫相关信号通路相关。基质评分、免疫评分和免疫细胞浸润也与 IGFBP7 和 LGG 的预后相关。
IGFBP7 而不是 PDGFRA 是胶质母细胞瘤的理想预后标志物和治疗靶点。
