Clinical Significance and Immune Landscape of a Pyroptosis-Derived LncRNA Signature for Glioblastoma.
Clinical Significance and Immune Landscape of a Pyroptosis-Derived LncRNA Signature for Glioblastoma.
复制标题
DOI：
10.3389/fcell.2022.805291
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Xing Z;Liu Z;Fu X;Zhou S;Liu L;Dang Q;Guo C;Ge X;Lu T;Zheng Y;Dai L;Han X;Wang X
前言：最近发现上睑下垂与肿瘤的发生和发展有关，包括胶质母细胞瘤(GBM)。本研究旨在探讨上睑下垂相关转录因子(PRL)在基底膜中的表达及其临床意义。方法：从TCGA和CGGA数据库中检索到3个独立的队列。采用共识聚类和加权基因共表达网络分析(WGCNA)鉴定PRL。LASSO算法被用来在三个独立的队列中开发和验证与热下垂相关的lncRNA签名(PRLS)。并对PRLS的分子特征、临床意义、肿瘤微环境、免疫检查点特征以及化疗和免疫治疗的益处等方面进行了探讨。结果：在WGCNA框架中，提取了与上睑下垂高度相关的关键模块，用于识别PRL。单变量COX分析进一步揭示了催乳素与总存活率之间的关系。根据PRLS的表达谱，PRLS最初是在TCGA队列中开发的(n=6143)，然后在两个CGGA队列中进行验证(n=10374)。多因素COX分析表明，我们的PRLS模型是一个独立的危险因素。更重要的是，这一征象在预测1、3和5年后的预后方面表现出稳定和准确的表现，所有AUC都在0.7以上。决策曲线分析也表明，我们的签名具有良好的临床应用前景。此外，PRLS评分高的患者免疫浸润更丰富，免疫检查点基因的表达更高，对免疫治疗的反应较好，但对化疗的反应较差。结论：构建了一种新的具有稳健性能的与下垂相关的lncRNA签名，并在多个队列中进行了验证。这一特征为临床治疗和精确治疗提供了新的视角。
Introduction: Pyroptosis was recently implicated in the initiation and progression of tumors, including glioblastoma (GBM). This study aimed to explore the clinical significance of pyroptosis-related lncRNAs (PRLs) in GBM. Methods: Three independent cohorts were retrieved from the TCGA and CGGA databases. The consensus clustering and weighted gene coexpression network analysis (WGCNA) were applied to identify PRLs. The LASSO algorithm was employed to develop and validate a pyroptosis-related lncRNA signature (PRLS) in three independent cohorts. The molecular characteristics, clinical significances, tumor microenvironment, immune checkpoints profiles, and benefits of chemotherapy and immunotherapy regarding to PRLS were also explored. Results: In the WGCNA framework, a key module that highly correlated with pyroptosis was extracted for identifying PRLs. Univariate Cox analysis further revealed the associations between PRLs and overall survival. Based on the expression profiles of PRLs, the PRLS was initially developed in TCGA cohort (n = 143) and then validated in two CGGA cohorts (n = 374). Multivariate Cox analysis demonstrated that our PRLS model was an independent risk factor. More importantly, this signature displayed a stable and accurate performance in predicting prognosis at 1, 3, and 5 years, with all AUCs above 0.7. The decision curve analysis also indicated that our signature had promising clinical application. In addition, patients with high PRLS score suggested a more abundant immune infiltration, higher expression of immune checkpoint genes, and better response to immunotherapy but worse to chemotherapy. Conclusion: A novel pyroptosis-related lncRNA signature with a robust performance was constructed and validated in multiple cohorts. This signature provided new perspectives for clinical management and precise treatments of GBM.
登录
查看更多内容
影响因子：
4.7
作者：
Liu Z;Zhang Y;Dang Q;Wu K;Jiao D;Li Z;Sun Z;Han X
通讯作者：
Han X
影响因子：
4.7
作者：
Oronsky B;Reid TR;Oronsky A;Sandhu N;Knox SJ
通讯作者：
Knox SJ
影响因子：
7.3
作者：
Liu Z;Lu T;Li J;Wang L;Xu K;Dang Q;Liu L;Guo C;Jiao D;Sun Z;Han X
通讯作者：
Han X
影响因子：
3.7
作者：
Liu Z;Liu L;Jiao D;Guo C;Wang L;Li Z;Sun Z;Zhao Y;Han X
通讯作者：
Han X
影响因子：
4.7
作者：
Niu X;Sun J;Meng L;Fang T;Zhang T;Jiang J;Li H
通讯作者：
Li H