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衰老相关泛素化基因的血细胞DNA甲基化可预测早期结直肠癌的发病

Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene Can Predict the Onset of Early Stage Colorectal Cancer.

作者信息

Quan Yuan, Liang Fengji, Wu Deqing, Yao Xueqing, Hu Zhihuang, Zhu Yuexing, Chen Ying, Wu Andong, Tang Danian, Huang Bingyang, Xu Ruifeng, Lyu Zejian, Yan Qian, Luo Lang, Ning Zhengzhi, Li Yong, Xiong Jianghui

机构信息

School of Computer Science and Technology, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, China.

Lab of Epigenetics and Advanced Health Technology, Space Science and Technology Institute (Shenzhen), Shenzhen, China.

出版信息

Front Oncol. 2020 Nov 27;10:544330. doi: 10.3389/fonc.2020.544330. eCollection 2020.

DOI:10.3389/fonc.2020.544330
PMID:33330022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7729090/
Abstract

There is a body of evidence that the aging immune system is linked to cancer. In this study, with aging- and immune-related DNA methylation data, we investigated the DNA methylation regulation changes in promoters with other regions of genes during aging and their association with the immune-cell proportion in the circulating whole blood of individuals. The analyses for aging- and CD4+ T cell proportion-derived differential genes showed that ubiquitination plays an important role in the aging immune system and tumorigenesis. Therefore, starting from a set of pre-annotated ubiquitination genes, we found that among the differentially ubiquitinated genes, , an E3 ubiquitin ligase with no reports on its function in immune cells and tumorigenesis, was significantly associated with both aging (P-value = 3.86e-06) and CD4+ T cell proportion (P-value = 1.97e-05) in circulating blood. By collecting a cohort of 100 colon cancer patients and 50 healthy individuals, we validated that the 1 exon DNA methylation of could predict the onset of early stage (AUC = 0.833, OR = 8.82) and all pTNM stages of colorectal cancer (AUC = 0.782, OR = 5.70). Thus, the epigenetically regulated ubiquitination machine plays an important role in immune aging and tumorigenesis.

摘要

有大量证据表明衰老的免疫系统与癌症有关。在本研究中，利用与衰老和免疫相关的DNA甲基化数据，我们调查了衰老过程中基因启动子与其他区域的DNA甲基化调控变化及其与个体循环全血中免疫细胞比例的关联。对衰老和CD4+T细胞比例衍生的差异基因的分析表明，泛素化在衰老免疫系统和肿瘤发生中起重要作用。因此，从一组预先注释的泛素化基因开始，我们发现， 在差异泛素化基因中，一种在免疫细胞和肿瘤发生中其功能尚无报道的E3泛素连接酶，与循环血液中的衰老（P值 = 3.86e - 06）和CD4+T细胞比例（P值 = 1.97e - 05）均显著相关。通过收集100名结肠癌患者和50名健康个体的队列，我们验证了 的1号外显子DNA甲基化可预测早期（AUC = 0.833，OR = 8.82）和所有pTNM分期的结直肠癌的发病（AUC = 0.782，OR = 5.70）。因此，表观遗传调控的泛素化机制在免疫衰老和肿瘤发生中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de3b/7729090/8661b99bbe88/fonc-10-544330-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de3b/7729090/8661b99bbe88/fonc-10-544330-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de3b/7729090/30fb156ab47c/fonc-10-544330-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de3b/7729090/1f0143f1d738/fonc-10-544330-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de3b/7729090/50580ff2d350/fonc-10-544330-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de3b/7729090/8661b99bbe88/fonc-10-544330-g005.jpg

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