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胶质瘤中TK1的多组学整合分析:一种用于预测、预防和个性化医疗方法的潜在生物标志物。

Multi-Omics Integration Analysis of TK1 in Glioma: A Potential Biomarker for Predictive, Preventive, and Personalized Medical Approaches.

作者信息

Shao Chuan, Wang Pan, Liao Bin, Gong Sheng, Wu Nan

机构信息

Graduate Institute, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.

Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, China.

出版信息

Brain Sci. 2023 Jan 30;13(2):230. doi: 10.3390/brainsci13020230.

Abstract

Multi-omics expression datasets obtained from multiple public databases were used to elucidate the biological function of TK1 and its effects on clinical outcomes. The Kaplan-Meier curve, a predictive nomogram mode, and the time-dependent receiver operating characteristic (ROC) curve were established to assess the role of TK1 expression in glioma prognosis. TK1 was overexpressed in glioma compared with normal samples, and patients with elevated expression of TK1 had poor overall survival. The ROC curves indicated a high diagnostic value of TK1 expression in patients of glioma; the areas under the ROC curve (AUC) were 0.682, 0.735, and 0.758 for 1 year, 3 years, and 5 years of glioma survival, respectively. For a model based on TK1 expression and other clinical characteristics, the values of AUC were 0.864, 0.896, and 0.898 for 1 year, 3 years, and 5 years, respectively. Additionally, the calibration curve indicated that the predicted and observed areas at 1 year, 3 years, and 5 years of survival were in excellent agreement. Three types of TK1 alterations-missense mutations, splice mutations, and amplifications-were identified in 25 of 2706 glioma samples. The TK1-altered group had better overall survival than the unaltered group. Single-cell function analysis showed that TK1 was positively associated with proliferation, the cell cycle, DNA repair, DNA damage, and epithelial-mesenchymal transition in glioma. Immunoinfiltration analysis indicated that TK1 expression might play different roles in low-grade glioma and glioblastoma multiforme tumor microenvironments, but TK1 expression was positively associated with activated CD4 and Th2, regardless of tumor grade. In summary, our findings identified TK1 as a novel marker for predicting clinical outcomes and a potential target for glioma.

摘要

从多个公共数据库获得的多组学表达数据集用于阐明TK1的生物学功能及其对临床结局的影响。建立了Kaplan-Meier曲线、预测列线图模型和时间依赖性受试者工作特征(ROC)曲线,以评估TK1表达在胶质瘤预后中的作用。与正常样本相比,TK1在胶质瘤中过表达,TK1表达升高的患者总生存期较差。ROC曲线表明TK1表达在胶质瘤患者中具有较高的诊断价值;胶质瘤生存1年、3年和5年的ROC曲线下面积(AUC)分别为0.682、0.735和0.758。对于基于TK1表达和其他临床特征的模型,1年、3年和5年的AUC值分别为0.864、0.896和0.898。此外,校准曲线表明生存1年、3年和5年的预测和观察区域高度一致。在2706例胶质瘤样本中的25例中鉴定出三种类型的TK1改变——错义突变、剪接突变和扩增。TK1改变组的总生存期优于未改变组。单细胞功能分析表明,TK1与胶质瘤中的增殖、细胞周期、DNA修复、DNA损伤和上皮-间质转化呈正相关。免疫浸润分析表明,TK1表达在低级别胶质瘤和多形性胶质母细胞瘤肿瘤微环境中可能发挥不同作用,但无论肿瘤级别如何,TK1表达均与活化的CD4和Th2呈正相关。总之,我们的研究结果确定TK1是预测临床结局的新型标志物和胶质瘤的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53b5/9954725/c6ba4f025b79/brainsci-13-00230-g001.jpg

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