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炎症背景下基因表达模式的泛癌分析

The pan-cancer analysis of gene expression patterns in the context of inflammation.

作者信息

Yu Xuexin, Lian Baofeng, Wang Lihong, Zhang Yan, Dai Enyu, Meng Fanlin, Liu Dianming, Wang Shuyuan, Liu Xinyi, Wang Jing, Li Xia, Jiang Wei

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, China.

出版信息

Mol Biosyst. 2014 Jul 29;10(9):2270-6. doi: 10.1039/c4mb00258j.

Abstract

Although several studies have investigated the essential roles of inflammation in tumor progression, not many have systematically analyzed gene expression patterns across diverse cancers in the context of inflammation. In this study, in order to better understand the inflammatory scenario, we initially constructed the inflammatory timeline (IT) based on two gene expression profiles during inflammatory progression (inflammatory bowel disease and Helicobacter pylori infection). Then, we separately identified the differentially expressed genes (DEGs) from 25 cancer-related microarray data. By comparing the distributions of DEGs in the IT, we identified three novel pan-cancer gene expression patterns. In the first pattern, the up-regulated genes in cancers were over-expressed in the early phase of inflammation, while the down-regulated genes were over-expressed in the late phase of inflammation. The second pattern was the opposite of the first one. The third pattern appeared to be transitional between the first and second patterns. We found that some cancers with different tissue origins have similar gene expression patterns. Finally, we identified two sets of tissue-independent inflammatory signatures that were over-expressed in early and late phases of inflammation, respectively. The dominant biological processes of early inflammatory signatures were cell proliferation, DNA replication, and DNA repair, whereas the late inflammatory signatures were reflective of innate immune response, neutrophil migration, and antigen processing. These inflammatory signatures may be useful to predict gene expression patterns in human cancers. Therefore, the pan-cancer analysis of gene expression patterns in the context of inflammation provides a novel insight into cancers and an unprecedented opportunity to develop new therapies.

摘要

尽管有多项研究探讨了炎症在肿瘤进展中的重要作用,但在炎症背景下系统分析多种癌症基因表达模式的研究并不多。在本研究中,为了更好地了解炎症情况,我们首先基于炎症进展过程中的两个基因表达谱(炎症性肠病和幽门螺杆菌感染)构建了炎症时间线(IT)。然后,我们从25个癌症相关的微阵列数据中分别鉴定出差异表达基因(DEG)。通过比较DEG在IT中的分布,我们确定了三种新的泛癌基因表达模式。在第一种模式中,癌症中上调的基因在炎症早期过度表达,而下调的基因在炎症晚期过度表达。第二种模式与第一种相反。第三种模式似乎是第一种和第二种模式之间的过渡。我们发现一些组织来源不同的癌症具有相似的基因表达模式。最后,我们确定了两组与组织无关的炎症特征,它们分别在炎症的早期和晚期过度表达。早期炎症特征的主要生物学过程是细胞增殖、DNA复制和DNA修复,而晚期炎症特征反映了先天免疫反应、中性粒细胞迁移和抗原加工。这些炎症特征可能有助于预测人类癌症中的基因表达模式。因此,在炎症背景下对基因表达模式进行泛癌分析为癌症研究提供了新的见解,并为开发新疗法提供了前所未有的机会。

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