Integrative analysis reveals the functional implications and clinical relevance of pyroptosis in low-grade glioma.
Integrative analysis reveals the functional implications and clinical relevance of pyroptosis in low-grade glioma.
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DOI：
10.1038/s41598-022-08619-w
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发表时间：
2022-03-16
影响因子：
4.6
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Shen L;Li Y;Li N;Zhao Y;Zhou Q;Shen L;Li Z
使用中国胶质瘤基因组图谱（训练数据集）和癌症基因组图谱（验证数据集），我们发现低级别胶质瘤可以根据30个焦亡基因分为两个分子亚类。第1组的免疫细胞和免疫功能评分高于第2组，预后较差。我们建立了一个基于10个焦亡基因的预后模型;该模型可以预测胶质瘤的总生存率，并在一个独立的数据集中得到了很好的验证。与低危组相比，高危组的免疫细胞和免疫功能评分相对较高，而焦亡基因的DNA甲基化水平较低。在高风险组和低风险组之间，焦亡基因改变没有显著差异。竞争性内源性RNA（ceRNA）调控网络揭示了低级别胶质瘤中不同风险组的lncRNA-miRNA-mRNA调控模式。确定了五对靶基因和药物。在体外，CASP 8沉默抑制胶质瘤细胞的迁移和侵袭。Pyroptosis基因的表达可以反映低级别胶质瘤亚类的分子生物学和临床特征。开发的预后模型可以预测总生存期和区分患者的分子改变。我们的综合分析可以为改善低级别胶质瘤患者的风险管理和治疗提供有价值的指导。
Using the Chinese Glioma Genome Atlas (training dataset) and The Cancer Genome Atlas (validation dataset), we found that low-grade gliomas can be divided into two molecular subclasses based on 30 pyroptosis genes. Cluster 1 presented higher immune cell and immune function scores and poorer prognosis than Cluster 2. We established a prognostic model based on 10 pyroptosis genes; the model could predict overall survival in glioma and was well validated in an independent dataset. The high-risk group had relatively higher immune cell and immune function scores and lower DNA methylation levels in pyroptosis genes than the low-risk group. There were no marked differences in pyroptosis gene alterations between the high- and low-risk groups. The competing endogenous RNA (ceRNA) regulatory network uncovered the lncRNA–miRNA–mRNA regulation patterns of the different risk groups in low-grade glioma. Five pairs of target genes and drugs were identified. In vitro, CASP8 silencing inhibited the migration and invasion of glioma cells. The expression of pyroptosis genes can reflect the molecular biological and clinical features of low-grade glioma subclasses. The developed prognostic model can predict overall survival and distinguish molecular alterations in patients. Our integrated analyses could provide valuable guidelines for improving risk management and therapy for low-grade glioma patients.
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影响因子：
4.1
作者：
Minami N;Tanaka K;Sasayama T;Kohmura E;Saya H;Sampetrean O
通讯作者：
Sampetrean O
影响因子：
64.8
作者：
Shi, Jianjin;Zhao, Yue;Shao, Feng
通讯作者：
Shao, Feng
DOI：
10.31557/apjcp.2020.21.12.3469
发表时间：
2020-12-01
期刊：
Asian Pacific journal of cancer prevention : APJCP
影响因子：
--
作者：
Alahverdi A;Arefian E;Soleimani M;Ai J;Yousefi-Ahmadipour A;Babaei A;Islam MS;Ebrahimi-Barough S
通讯作者：
Ebrahimi-Barough S
影响因子：
8.7
作者：
Man SM;Kanneganti TD
通讯作者：
Kanneganti TD
影响因子：
3.7
作者：
Coniglio SJ;Segall JE
通讯作者：
Segall JE