Li Yingjie, Sun Hong
Shanghai Engineering Research Center for Big Data in Pediatric Precision Medicine, Center for Biomedical Informatics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Sci Rep. 2025 Feb 17;15(1):5806. doi: 10.1038/s41598-025-90658-0.
Gliomas have highly variable clinical outcomes that are not adequately predicted on the basis of histologic class nor genetic markers. We performed a comprehensive analysis that integrated multi-omics datasets to elucidate factors influencing glioma prognosis. We detected 17 grade-related genes different in expression between LGG and GBM cohorts. By combining multi-layer information including genetic markers, DNA methylation and gene expression, we constructed two gene networks of relations from the grade-related genes. From the networks, we identified 178 prognostic genes whose activity states, in terms of DNA methylation and gene expression level, are relevant to prognostic outcomes of gliomas, with low activity associated with better outcomes. The efficacy of these 178 genes' activity states as prognostic factors beyond genetic markers, i.e. IDH1 or PTEN gene mutations, was validated externally. Among the 178 prognostic genes, we validated roles in gliomas for 121 genes from previous literature, and more importantly, we identified 67 novel candidate genes for glioma research. Expression of these 178 genes was particularly pronounced during fetal development in various brain regions. Our findings provide clues for understanding glioma prognosis and highlight some novel glioma-associated genes that warrant further investigation.
神经胶质瘤具有高度可变的临床结果，基于组织学分类或基因标志物均无法充分预测这些结果。我们进行了一项综合分析，整合了多组学数据集，以阐明影响神经胶质瘤预后的因素。我们检测到17个在低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）队列之间表达不同的与分级相关的基因。通过结合包括基因标志物、DNA甲基化和基因表达在内的多层信息，我们从与分级相关的基因构建了两个关系基因网络。从这些网络中，我们确定了178个预后基因，其在DNA甲基化和基因表达水平方面的活性状态与神经胶质瘤的预后结果相关，活性低与较好的结果相关。这些178个基因活性状态作为预后因素的有效性，超越了基因标志物，即异柠檬酸脱氢酶1（IDH1）或磷酸酶和张力蛋白同源物（PTEN）基因突变，在外部得到了验证。在这178个预后基因中，我们从先前的文献中验证了121个基因在神经胶质瘤中的作用，更重要的是，我们确定了67个神经胶质瘤研究的新候选基因。这些178个基因的表达在胎儿发育期间在各个脑区尤为明显。我们的研究结果为理解神经胶质瘤的预后提供了线索，并突出了一些值得进一步研究的新型神经胶质瘤相关基因。
