Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer

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

doi:10.3389/fonc.2020.544330

Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer

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

^*Corresponding author for this work

Harbin Institute of Technology Shenzhen
Space Science and Technology Institute
China Astronaut Research and Training Center
Division of Thoracic Surgery
Fudan University
Beijing Hospital
Strategic Support Force Medical Center of PLA. No. 9
Ltd

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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 1^st 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.

Original language	English
Article number	544330
Journal	Frontiers in Oncology
Volume	10
DOIs	https://doi.org/10.3389/fonc.2020.544330
State	Published - 27 Nov 2020
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

DZIP3
E3 ubiquitin ligase
aging immune system
cancer screening
colon cancer
early detection
liquid biopsy

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10.3389/fonc.2020.544330

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Quan, Y., Liang, F., Wu, D., Yao, X., Hu, Z., Zhu, Y., Chen, Y., Wu, A., Tang, D., Huang, B., Xu, R., Lyu, Z., Yan, Q., Luo, L., Ning, Z., Li, Y., & Xiong, J. (2020). Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer. Frontiers in Oncology, 10, Article 544330. https://doi.org/10.3389/fonc.2020.544330

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title = "Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer",

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.",

keywords = "DZIP3, E3 ubiquitin ligase, aging immune system, cancer screening, colon cancer, early detection, liquid biopsy",

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

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Quan, Liang, Wu, Yao, Hu, Zhu, Chen, Wu, Tang, Huang, Xu, Lyu, Yan, Luo, Ning, Li and Xiong.",

year = "2020",

month = nov,

day = "27",

doi = "10.3389/fonc.2020.544330",

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T1 - Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer

AU - Quan, Yuan

AU - Liang, Fengji

AU - Wu, Deqing

AU - Yao, Xueqing

AU - Hu, Zhihuang

AU - Zhu, Yuexing

AU - Chen, Ying

AU - Wu, Andong

AU - Tang, Danian

AU - Huang, Bingyang

AU - Xu, Ruifeng

AU - Lyu, Zejian

AU - Yan, Qian

AU - Luo, Lang

AU - Ning, Zhengzhi

AU - Li, Yong

AU - Xiong, Jianghui

PY - 2020/11/27

Y1 - 2020/11/27

N2 - 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.

AB - 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.

KW - DZIP3

KW - E3 ubiquitin ligase

KW - aging immune system

KW - cancer screening

KW - colon cancer

KW - early detection

KW - liquid biopsy

UR - https://www.scopus.com/pages/publications/85097495490

U2 - 10.3389/fonc.2020.544330

DO - 10.3389/fonc.2020.544330

M3 - 文章

AN - SCOPUS:85097495490

SN - 2234-943X

VL - 10

JO - Frontiers in Oncology

JF - Frontiers in Oncology

M1 - 544330

ER -

Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer

Abstract

UN SDGs

Keywords

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