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炎症衰老时钟:一种用于表征胶质母细胞瘤患者亚型并预测其总生存期的癌症时钟。

Inflammatory aging clock: A cancer clock to characterize the patients' subtypes and predict the overall survival in glioblastoma.

作者信息

Zhu Lei, Wang Feng, Huang Jiannan, Wang He, Wang Guangxue, Jiang Jianxin, Li Qinchuan

机构信息

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Department of Thoracic Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Front Genet. 2022 Aug 11;13:925469. doi: 10.3389/fgene.2022.925469. eCollection 2022.

Abstract

Many biological clocks related to aging have been linked to the development of cancer. A recent study has identified that the inflammatory aging clock was an excellent indicator to track multiple diseases. However, the role of the inflammatory aging clock in glioblastoma (GBM) remains to be explored. This study aimed to investigate the expression patterns and the prognostic values of inflammatory aging (iAge) in GBM, and its relations with stem cells. Inflammation-related genes (IRG) and their relations with chronological age in normal samples from the Cancer Genome Atlas (TCGA) were identified by the Spearman correlation analysis. Then, we calculated the iAge and computed their correlations with chronological age in 168 patients with GBM. Next, iAge was applied to classify the patients into high- and low-iAge subtypes. Next, the survival analysis was performed. In addition, the correlations between iAge and stem cell indexes were evaluated. Finally, the results were validated in an external cohort. Thirty-eight IRG were significantly associated with chronological age (|coefficient| > 0.5), and were used to calculate the iAge. Correlation analysis showed that iAge was positively correlated with chronological age. Enrichment analysis demonstrated that iAge was highly associated with immune cells and inflammatory activities. Survival analysis showed the patients in the low-iAge subtype had significantly better overall survival (OS) than those in the high-iAge subtype ( < 0.001). In addition, iAge outperformed the chronological age in revealing the correlations with stem cell stemness. External validation demonstrated that iAge was an excellent method to classify cancer subtypes and predict survival in patients with GBM. Inflammatory aging clock may be involved in the GBM potential influences on immune-related activities. iAge could be used as biomarkers for predicting the OS and monitoring the stem cell.

摘要

许多与衰老相关的生物钟都与癌症的发生发展有关。最近的一项研究发现,炎症衰老生物钟是追踪多种疾病的一个很好的指标。然而,炎症衰老生物钟在胶质母细胞瘤(GBM)中的作用仍有待探索。本研究旨在探讨炎症衰老(iAge)在GBM中的表达模式、预后价值及其与干细胞的关系。通过Spearman相关分析确定了癌症基因组图谱(TCGA)中正常样本中炎症相关基因(IRG)及其与实足年龄的关系。然后,我们计算了168例GBM患者的iAge,并计算了它们与实足年龄的相关性。接下来,应用iAge将患者分为高iAge亚型和低iAge亚型。接着,进行生存分析。此外,还评估了iAge与干细胞指标之间的相关性。最后,在一个外部队列中对结果进行了验证。38个IRG与实足年龄显著相关(|系数|>0.5),并用于计算iAge。相关分析表明,iAge与实足年龄呈正相关。富集分析表明,iAge与免疫细胞和炎症活动高度相关。生存分析显示,低iAge亚型患者的总生存期(OS)明显优于高iAge亚型患者(<0.001)。此外,在揭示与干细胞干性的相关性方面,iAge优于实足年龄。外部验证表明,iAge是一种很好的方法,可以对癌症亚型进行分类并预测GBM患者的生存情况。炎症衰老生物钟可能参与了GBM对免疫相关活动的潜在影响。iAge可用作预测OS和监测干细胞的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b53d/9402943/5c9099c00e95/fgene-13-925469-g001.jpg

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