Wu Chenxing, Song Hongwang, Fu Xiaojun, Li Shouwei, Jiang Tao
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Biomed Res Int. 2020 Mar 21;2020:1086792. doi: 10.1155/2020/1086792. eCollection 2020.
Glioma is the most common and lethal tumor in the central nervous system (CNS). More than 70% of WHO grade II/III gliomas were found to harbor isocitrate dehydrogenase (IDH) mutations which generated targetable metabolic vulnerabilities. Focusing on the metabolic vulnerabilities, some targeted therapies, such as NAMPT, have shown significant effects in preclinical and clinical trials.
We explored the TCGA as well as CGGA database and analyzed the RNA-seq data of lower grade gliomas (LGG) with the method of weighted correlation network analysis (WGCNA). Differential expressed genes were screened, and coexpression relationships were grouped together by performing average linkage hierarchical clustering on the topological overlap. Clinical data were used to conduct Kaplan-Meier analysis.
In this study, we identified ACAA2 as a prognostic factor in IDH mutation lower grade glioma with the method of weighted correlation network analysis (WGCNA). The difference of ACAA2 gene expressions between the IDH wild-type (IDH-WT) group and the IDH mutant (IDH-MUT) group suggested that there may be different potential targeted therapies based on the fatty acid metabolic vulnerabilities, which promoted the personalized treatment for LGG patients.
胶质瘤是中枢神经系统（CNS）中最常见且致命的肿瘤。超过70%的世界卫生组织（WHO）二级/三级胶质瘤被发现携带异柠檬酸脱氢酶（IDH）突变，这些突变产生了可靶向的代谢脆弱性。针对这些代谢脆弱性，一些靶向治疗，如NAMPT，已在临床前和临床试验中显示出显著效果。
我们探索了TCGA以及CGGA数据库，并采用加权基因共表达网络分析（WGCNA）方法分析了低级别胶质瘤（LGG）的RNA测序数据。筛选差异表达基因，并通过对拓扑重叠进行平均连锁层次聚类将共表达关系分组。利用临床数据进行Kaplan-Meier分析。
在本研究中，我们采用加权基因共表达网络分析（WGCNA）方法将ACAA2鉴定为IDH突变型低级别胶质瘤的一个预后因素。IDH野生型（IDH-WT）组和IDH突变型（IDH-MUT）组之间ACAA2基因表达的差异表明，基于脂肪酸代谢脆弱性可能存在不同的潜在靶向治疗方法，这促进了LGG患者的个性化治疗。
