Circadian Regulation Patterns With Distinct Immune Landscapes in Gliomas Aid in the Development of a Risk Model to Predict Prognosis and Therapeutic Response.
Circadian Regulation Patterns With Distinct Immune Landscapes in Gliomas Aid in the Development of a Risk Model to Predict Prognosis and Therapeutic Response.
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神经胶质瘤中具有独特免疫景观的昼夜节律调节模式有助于开发预测预后和治疗反应的风险模型
DOI：
10.3389/fimmu.2021.797450
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发表时间：
2021
影响因子：
7.3
通讯作者：
Shu M
中科院分区：
文献类型：
--
作者：
Tian R;Li Y;Shu M
肿瘤发生中的昼夜节律破坏已被广泛研究，但昼夜节律（CR）如何影响肿瘤微环境（TME）的形成以及TME与癌细胞之间的串扰在很大程度上是未知的，特别是在胶质瘤中。在此，我们回顾性分析了来自公共数据库的胶质瘤患者的转录组数据和临床参数，以探索昼夜节律控制的肿瘤异质性和胶质瘤中TME的特征。首先，我们率先构建了一个CR基因集整理从五个数据集和回顾文献。根据CR基因的表达情况，采用无监督聚类方法识别出两个具有不同CR模式的CR聚类。值得注意的是，CR簇B的特征在于富集的髓样细胞和激活的免疫相关通路。其次，我们应用主成分分析构建CR评分来量化个体肿瘤的CR模式，并通过单变量和多变量回归分析结合列线图进一步验证CR评分在预后预测中的功能。CR评分不仅可以作为预测胶质瘤患者预后的独立因素，而且可以指导患者选择合适的治疗策略：免疫治疗或化疗。具有高CR评分的胶质瘤患者可能对免疫检查点阻断有反应，而具有低CR评分的患者可能从化疗中获益。在这项研究中，我们发现，昼夜节律调节肿瘤的异质性，TME的多样性和复杂性，在胶质瘤。评估单个肿瘤的CR评分将有助于更好地了解每个患者的肿瘤免疫状态，提高预后预测的准确性，并提出更有效的治疗方案。
Circadian disruption in tumorigenesis has been extensively studied, but how circadian rhythm (CR) affects the formation of tumor microenvironment (TME) and the crosstalk between TME and cancer cells is largely unknown, especially in gliomas. Herein, we retrospectively analyzed transcriptome data and clinical parameters of glioma patients from public databases to explore circadian rhythm-controlled tumor heterogeneity and characteristics of TME in gliomas. Firstly, we pioneered the construction of a CR gene set collated from five datasets and review literatures. Unsupervised clustering was used to identify two CR clusters with different CR patterns on the basis of the expression of CR genes. Remarkably, the CR cluster-B was characterized by enriched myeloid cells and activated immune-related pathways. Next, we applied principal component analysis to construct a CRscore to quantify CR patterns of individual tumors, and the function of the CRscore in prognostic prediction was further verified by univariate and multivariate regression analyses in combination with a nomogram. The CRscore could not only be an independent factor to predict prognosis of glioma patients but also guide patients to choose suitable treatment strategies: immunotherapy or chemotherapy. A glioma patient with a high CRscore might respond to immune checkpoint blockade, whereas one with a low CRscore could benefit from chemotherapy. In this study, we revealed that circadian rhythms modulated tumor heterogeneity, TME diversity, and complexity in gliomas. Evaluating the CRscore of an individual tumor would contribute to gaining a greater understanding of the tumor immune status of each patient, enhancing the accuracy of prognostic prediction, and suggesting more effective treatment options.
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影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
DOI：
10.1073/pnas.1800431115
发表时间：
2018-09-04
影响因子：
11.1
作者：
Early JO;Menon D;Wyse CA;Cervantes-Silva MP;Zaslona Z;Carroll RG;Palsson-McDermott EM;Angiari S;Ryan DG;Corcoran SE;Timmons G;Geiger SS;Fitzpatrick DJ;O'Connell D;Xavier RJ;Hokamp K;O'Neill LAJ;Curtis AM
通讯作者：
Curtis AM
影响因子：
14.9
作者：
Martens M;Ammar A;Riutta A;Waagmeester A;Slenter DN;Hanspers K;A Miller R;Digles D;Lopes EN;Ehrhart F;Dupuis LJ;Winckers LA;Coort SL;Willighagen EL;Evelo CT;Pico AR;Kutmon M
通讯作者：
Kutmon M
DOI：
10.1126/science.aao0318
发表时间：
2018-03-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mure LS;Le HD;Benegiamo G;Chang MW;Rios L;Jillani N;Ngotho M;Kariuki T;Dkhissi-Benyahya O;Cooper HM;Panda S
通讯作者：
Panda S