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大规模转录组学驱动的方法揭示了[具体基因]的过表达是胶质母细胞瘤患者生存预后不良的生物标志物。 (注:原文中“as a Poor Survival Prognosis Biomarker in Glioblastoma”前缺少具体基因,这里用[具体基因]表示)

Large-Scale Transcriptomics-Driven Approach Revealed Overexpression of as a Poor Survival Prognosis Biomarker in Glioblastoma.

作者信息

Sorokin Maxim, Raevskiy Mikhail, Zottel Alja, Šamec Neja, Skoblar Vidmar Marija, Matjašič Alenka, Zupan Andrej, Mlakar Jernej, Suntsova Maria, Kuzmin Denis V, Buzdin Anton, Jovčevska Ivana

机构信息

European Organization for Research and Treatment of Cancer (EORTC), Biostatistics and Bioinformatics Subgroup, 1000 Brussels, Belgium.

World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, 119991 Moscow, Russia.

出版信息

Cancers (Basel). 2021 Jul 8;13(14):3419. doi: 10.3390/cancers13143419.

Abstract

Glioblastoma is the most common and malignant brain malignancy worldwide, with a 10-year survival of only 0.7%. Aggressive multimodal treatment is not enough to increase life expectancy and provide good quality of life for glioblastoma patients. In addition, despite decades of research, there are no established biomarkers for early disease diagnosis and monitoring of patient response to treatment. High throughput sequencing technologies allow for the identification of unique molecules from large clinically annotated datasets. Thus, the aim of our study was to identify significant molecular changes between short- and long-term glioblastoma survivors by transcriptome RNA sequencing profiling, followed by differential pathway-activation-level analysis. We used data from the publicly available repositories The Cancer Genome Atlas (TCGA; number of annotated cases = 135) and Chinese Glioma Genome Atlas (CGGA; number of annotated cases = 218), and experimental clinically annotated glioblastoma tissue samples from the Institute of Pathology, Faculty of Medicine in Ljubljana corresponding to 2-58 months overall survival (n = 16). We found one differential gene for long noncoding RNA whose overexpression showed correlation to poor patient OS. Moreover, we identified overlapping sets of congruently regulated differential genes involved in cell growth, division, and migration, structure and dynamics of extracellular matrix, DNA methylation, and regulation through noncoding RNAs. Gene ontology analysis can provide additional information about the function of protein- and nonprotein-coding genes of interest and the processes in which they are involved. In the future, this can shape the design of more targeted therapeutic approaches.

摘要

胶质母细胞瘤是全球最常见且恶性程度最高的脑恶性肿瘤,10年生存率仅为0.7%。积极的多模式治疗不足以提高胶质母细胞瘤患者的预期寿命并提供良好的生活质量。此外,尽管经过数十年研究,但仍没有用于早期疾病诊断和监测患者治疗反应的既定生物标志物。高通量测序技术能够从大量临床注释数据集中识别独特分子。因此,我们研究的目的是通过转录组RNA测序分析,随后进行差异通路激活水平分析,来识别短期和长期胶质母细胞瘤幸存者之间的显著分子变化。我们使用了来自公开可用数据库“癌症基因组图谱(TCGA;注释病例数 = 135)”和“中国胶质瘤基因组图谱(CGGA;注释病例数 = 218)”的数据,以及来自卢布尔雅那医学院病理学研究所的实验性临床注释胶质母细胞瘤组织样本,这些样本对应的总生存期为2至58个月(n = 16)。我们发现了一个长链非编码RNA的差异基因,其过表达与患者较差的总生存期相关。此外,我们确定了在细胞生长、分裂和迁移、细胞外基质的结构和动态、DNA甲基化以及通过非编码RNA进行调控等方面涉及的一组重叠的一致性调控差异基因。基因本体分析可以提供有关感兴趣的蛋白质编码基因和非蛋白质编码基因的功能以及它们所参与过程的额外信息。未来,这可以为更具针对性的治疗方法设计提供指导。

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