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通过综合分析不同癌症转录数据揭示个体水平的预后相关途径。

Revealing Prognosis-Related Pathways at the Individual Level by a Comprehensive Analysis of Different Cancer Transcription Data.

机构信息

College of Agriculture, Nanjing Agricultural University, Nanjing 210095, China.

Department of Mathematics, College of Science, Nanjing Agricultural University, Nanjing 210095, China.

出版信息

Genes (Basel). 2020 Oct 29;11(11):1281. doi: 10.3390/genes11111281.

Abstract

Identifying perturbed pathways at an individual level is important to discover the causes of cancer and develop individualized custom therapeutic strategies. Though prognostic gene lists have had success in prognosis prediction, using single genes that are related to the relevant system or specific network cannot fully reveal the process of tumorigenesis. We hypothesize that in individual samples, the disruption of transcription homeostasis can influence the occurrence, development, and metastasis of tumors and has implications for patient survival outcomes. Here, we introduced the individual-level pathway score, which can measure the correlation perturbation of the pathways in a single sample well. We applied this method to the expression data of 16 different cancer types from The Cancer Genome Atlas (TCGA) database. Our results indicate that different cancer types as well as their tumor-adjacent tissues can be clearly distinguished by the individual-level pathway score. Additionally, we found that there was strong heterogeneity among different cancer types and the percentage of perturbed pathways as well as the perturbation proportions of tumor samples in each pathway were significantly different. Finally, the prognosis-related pathways of different cancer types were obtained by survival analysis. We demonstrated that the individual-level pathway score (iPS) is capable of classifying cancer types and identifying some key prognosis-related pathways.

摘要

确定个体水平上受干扰的途径对于发现癌症的原因和制定个体化的治疗策略非常重要。虽然预后基因列表在预后预测方面取得了成功,但使用与相关系统或特定网络相关的单个基因并不能完全揭示肿瘤发生的过程。我们假设在个体样本中,转录组稳态的破坏会影响肿瘤的发生、发展和转移,并对患者的生存结果产生影响。在这里,我们引入了个体水平途径评分,它可以很好地衡量单个样本中途径的相关性扰动。我们将该方法应用于来自癌症基因组图谱(TCGA)数据库的 16 种不同癌症类型的表达数据。我们的结果表明,不同的癌症类型及其肿瘤相邻组织可以通过个体水平途径评分来清晰地区分。此外,我们发现不同的癌症类型之间存在很强的异质性,以及受干扰途径的比例和每个途径中肿瘤样本的干扰比例也存在显著差异。最后,通过生存分析获得了不同癌症类型的预后相关途径。我们证明了个体水平途径评分(iPS)能够对癌症类型进行分类,并识别出一些关键的与预后相关的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f53/7692404/df17b87226df/genes-11-01281-g001.jpg

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