Department of Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, 830054, Urumqi, China.
The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.
Mol Med. 2023 May 14;29(1):64. doi: 10.1186/s10020-023-00652-3.
Low-grade gliomas (LGG) are a type of brain tumor that can be lethal, and it is essential to identify genes that are correlated with patient prognosis. In this study, we aimed to use CRISPR-cas9 screening data to identify key signaling pathways and develop a genetic signature associated with high-risk, low-grade glioma patients.
The study used CRISPR-cas9 screening data to identify essential genes correlated with cell survival in LGG. We used RNA-seq data to identify differentially expressed genes (DEGs) related to cell viability. Moreover, we used the least absolute shrinkage and selection operator (LASSO) method to construct a genetic signature for predicting overall survival in patients. We performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the Weighted correlation network analysis (WGCNA). Finally, the study used western blot, qRT-PCR, and IHC to detect the expression of hub genes from signature in clinical samples.
The study identified 145 overexpressed oncogenes in low-grade gliomas using the TCGA database. These genes were intersected with lethal genes identified in the CRISPR-cas9 screening data from Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct a genetic signature, and the Hippo signaling pathway was found to be the predominantly enriched pathway. The signature effectively distinguished between low- and high-risk patients, with high-risk patients showing a shorter overall survival duration. Differences in hub gene expression were found in different clinical samples, with the protein and mRNA expression of REP65 being significantly up-regulated in tumor cells. The study suggests that the Hippo signaling pathway may be a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including low-grade gliomas.
Our study identified a novel genetic signature associated with high-risk, LGG patients. We found that the Hippo signaling pathway was significantly enriched in this signature, indicating that it may be a critical regulator of tumor viability and proliferation in LGG. Targeting the Hippo pathway could be an innovative new strategy for treating LGG.
低级别胶质瘤（LGG）是一种致命的脑肿瘤，识别与患者预后相关的基因至关重要。在这项研究中，我们旨在使用 CRISPR-cas9 筛选数据来鉴定与高风险、低级别脑胶质瘤患者相关的关键信号通路，并开发一个遗传特征。
该研究使用 CRISPR-cas9 筛选数据来鉴定与 LGG 细胞存活相关的必需基因。我们使用 RNA-seq 数据来鉴定与细胞活力相关的差异表达基因（DEGs）。此外，我们使用最小绝对值收缩和选择算子（LASSO）方法构建用于预测患者总生存期的遗传特征。我们进行了富集分析，以鉴定由 DEGs、重叠基因和 WGCNA 共享的基因介导的途径。最后，该研究使用 Western blot、qRT-PCR 和 IHC 检测临床样本中签名的枢纽基因的表达。
该研究使用 TCGA 数据库在低级别胶质瘤中鉴定了 145 个过表达的癌基因。这些基因与 Depmap 数据库中 CRISPR-cas9 筛选数据中鉴定的致死基因相交，这些基因富集在 Hippo 途径中。使用 19 个基因构建遗传特征，发现 Hippo 信号通路是主要富集的通路。该特征有效地区分了低风险和高风险患者，高风险患者的总体生存期更短。不同临床样本中枢纽基因的表达存在差异，肿瘤细胞中 REP65 的蛋白和 mRNA 表达明显上调。该研究表明，Hippo 信号通路可能是肿瘤活力和增殖的关键调节剂，因此是治疗包括低级别胶质瘤在内的癌性脑肿瘤的一种创新新靶点。
我们的研究鉴定了一个与高风险、LGG 患者相关的新型遗传特征。我们发现 Hippo 信号通路在这个特征中显著富集，表明它可能是 LGG 中肿瘤活力和增殖的关键调节剂。靶向 Hippo 通路可能是治疗 LGG 的一种创新新策略。
