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- Title
Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer.
- Authors
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
- 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, DZIP3 , 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 1st exon DNA methylation of DZIP3 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.
- Subjects
DNA methylation; UBIQUITIN ligases; COLORECTAL cancer; BLOOD cells; UBIQUITINATION; HEREDITARY nonpolyposis colorectal cancer; IMMUNOSENESCENCE; P16 gene
- Publication
Frontiers in Oncology, 2020, Vol 11, pN.PAG
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2020.544330