Association of Circadian Clock Gene Expression with Glioma Tumor Microenvironment and Patient Survival.
Association of Circadian Clock Gene Expression with Glioma Tumor Microenvironment and Patient Survival.
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DOI：
10.3390/cancers13112756
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发表时间：
2021-06-02
期刊：
影响因子：
5.2
通讯作者：
Armstrong TS
中科院分区：
文献类型：
--
作者：
De La Cruz Minyety J;Shuboni-Mulligan DD;Briceno N;Young D Jr;Gilbert MR;Celiku O;Armstrong TS
胶质瘤是最常见的恶性原发性脑肿瘤，根据细胞来源和遗传特征进行分类，有助于预测预后和治疗敏感性。改善预后仍然是一个挑战;然而，时间生物学是未来工作的一个有前途的领域，因为生物钟基因与肿瘤生物学和多种癌症（包括神经胶质瘤）的结果有关。在这里，我们通过对13个生物钟基因的表达进行无监督聚类，研究了生物钟基因、IDH突变状态和胶质瘤患者预后之间的关系。我们进一步探索了时钟基因在肿瘤区域和细胞亚群中的表达，突出了肿瘤微环境在研究癌症昼夜节律中的重要性。我们的研究对于了解如何最好地靶向昼夜节律以改善神经肿瘤患者的预后非常重要。生物钟基因与癌症（包括神经胶质瘤）的临床结果有关。然而，这些研究并没有解释预测预后的既定标志物，包括异柠檬酸脱氢酶（IDH）的突变，这是大多数低级别胶质瘤和继发性高级别胶质瘤的特征。为了证明生物钟基因与神经胶质瘤结局之间的联系，同时考虑IDH突变状态，我们分析了多个公开可用的基因表达数据集。来自癌症基因组图谱的13个时钟基因转录组特征的无监督聚类显示了代表不同疾病状态的不同分子亚型，并通过Kaplan-Meier分析显示了这些组的差异预后。对这些组的进一步分析表明，低周期（PER）基因表达与不良预后和免疫信号通路的富集相关。这些发现促使人们在其他数据集中探索微环境和时钟基因之间的关系。发现生物钟基因表达在解剖学肿瘤位置和细胞类型中差异表达。因此，生物钟表达是胶质瘤中潜在的预测生物标志物，并且需要进一步的机制研究来阐明生物钟和微环境之间的联系。
Gliomas are the most common type of malignant primary brain tumors and are classified according to the cell of origin and genetic features, which can help predict the prognosis and treatment sensitivity. Improving the prognosis remains a challenge; however, chronobiology is a promising field for future works, as circadian clock genes are linked to the tumor biology and outcomes in multiple cancers, including glioma. Here, we examined the relationship of circadian clock genes, IDH mutational status, and prognosis in glioma patients by using unsupervised clustering of the expression of 13 clock genes. We further explored the expression of the clock genes across the tumor regions and cell subpopulations, highlighting the importance of the tumor microenvironment in researching circadian rhythms in cancer. Our research is important for understanding how best to target circadian rhythms to improve patient outcomes in neuro-oncology. Circadian clock genes have been linked to clinical outcomes in cancer, including gliomas. However, these studies have not accounted for established markers that predict the prognosis, including mutations in Isocitrate Dehydrogenase (IDH), which characterize the majority of lower-grade gliomas and secondary high-grade gliomas. To demonstrate the connection between circadian clock genes and glioma outcomes while accounting for the IDH mutational status, we analyzed multiple publicly available gene expression datasets. The unsupervised clustering of 13 clock gene transcriptomic signatures from The Cancer Genome Atlas showed distinct molecular subtypes representing different disease states and showed the differential prognosis of these groups by a Kaplan–Meier analysis. Further analyses of these groups showed that a low period (PER) gene expression was associated with the negative prognosis and enrichment of the immune signaling pathways. These findings prompted the exploration of the relationship between the microenvironment and clock genes in additional datasets. Circadian clock gene expression was found to be differentially expressed across the anatomical tumor location and cell type. Thus, the circadian clock expression is a potential predictive biomarker in glioma, and further mechanistic studies to elucidate the connections between the circadian clock and microenvironment are warranted.
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影响因子：
64.8
作者：
Capper D;Jones DTW;Sill M;Hovestadt V;Schrimpf D;Sturm D;Koelsche C;Sahm F;Chavez L;Reuss DE;Kratz A;Wefers AK;Huang K;Pajtler KW;Schweizer L;Stichel D;Olar A;Engel NW;Lindenberg K;Harter PN;Braczynski AK;Plate KH;Dohmen H;Garvalov BK;Coras R;Hölsken A;Hewer E;Bewerunge-Hudler M;Schick M;Fischer R;Beschorner R;Schittenhelm J;Staszewski O;Wani K;Varlet P;Pages M;Temming P;Lohmann D;Selt F;Witt H;Milde T;Witt O;Aronica E;Giangaspero F;Rushing E;Scheurlen W;Geisenberger C;Rodriguez FJ;Becker A;Preusser M;Haberler C;Bjerkvig R;Cryan J;Farrell M;Deckert M;Hench J;Frank S;Serrano J;Kannan K;Tsirigos A;Brück W;Hofer S;Brehmer S;Seiz-Rosenhagen M;Hänggi D;Hans V;Rozsnoki S;Hansford JR;Kohlhof P;Kristensen BW;Lechner M;Lopes B;Mawrin C;Ketter R;Kulozik A;Khatib Z;Heppner F;Koch A;Jouvet A;Keohane C;Mühleisen H;Mueller W;Pohl U;Prinz M;Benner A;Zapatka M;Gottardo NG;Driever PH;Kramm CM;Müller HL;Rutkowski S;von Hoff K;Frühwald MC;Gnekow A;Fleischhack G;Tippelt S;Calaminus G;Monoranu CM;Perry A;Jones C;Jacques TS;Radlwimmer B;Gessi M;Pietsch T;Schramm J;Schackert G;Westphal M;Reifenberger G;Wesseling P;Weller M;Collins VP;Blümcke I;Bendszus M;Debus J;Huang A;Jabado N;Northcott PA;Paulus W;Gajjar A;Robinson GW;Taylor MD;Jaunmuktane Z;Ryzhova M;Platten M;Unterberg A;Wick W;Karajannis MA;Mittelbronn M;Acker T;Hartmann C;Aldape K;Schüller U;Buslei R;Lichter P;Kool M;Herold-Mende C;Ellison DW;Hasselblatt M;Snuderl M;Brandner S;Korshunov A;von Deimling A;Pfister SM
通讯作者：
Pfister SM
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：
10.15586/codon.glioblastoma.2017.ch16
发表时间：
2017-01-01
期刊：
GLIOBLASTOMA
影响因子：
--
作者：
De Vleeschouwer, Steven;Bergers, Gabriele
通讯作者：
Bergers, Gabriele
影响因子：
4.2
作者：
Chaumeil, Myriam M.;Radoul, Marina;Ronen, Sabrina M.
通讯作者：
Ronen, Sabrina M.
影响因子：
5.3
作者：
Abe, M;Herzog, ED;Block, GD
通讯作者：
Block, GD