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Potential blood DNA methylation biomarker genes for diagnosis of liver fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease

Potential blood DNA methylation biomarker genes for diagnosis of liver fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease
Potential blood DNA methylation biomarker genes for diagnosis of liver fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease
Background and objective: This pilot study aimed to identify potential blood DNA methylation (BDM) biomarker genes for the diagnosis of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: We included a total of 16 NAFLD patients with significant (SLF, liver fibrosis stage ≥ 2) and 16 patients with non-significant liver fibrosis (NSLF, fibrosis stages 0–1). The association between BDM and liver fibrosis was analyzed. Genes were selected based on a stepwise-filtering with CpG islands containing significant differentially methylated probes. Results: The two groups of patients were distinguishable through both t-distributed stochastic neighbor embedding (t-SNE) analysis and unsupervised hierarchical clustering analysis based on their BDM status. BDM levels were significantly higher in the NSLF group than in the SLF group. The methylation levels in the island and shelf regions were also significantly higher in the NSLF group, as well as the methylation levels in the first exon, 3′-untranslated region, body, ExonBnd, non-intergenic region, transcription start site (TSS)1500, and TSS200 regions (all p < 0.05). BDM status was associated with greater histological liver fibrosis, but not with age, sex, or other histological features of NAFLD (p < 0.05). The methylation levels of the hypomethylated CpG island region of CISTR, IFT140, and RGS14 genes were increased in the NSLF group compared to the SLF group (all p < 0.05). Conclusion: BDM may stratify NAFLD patients with significant and non-significant liver fibrosis. The CISTR, IFT140, and RGS14 genes are potential novel candidate BDM biomarkers for liver fibrosis and these pilot data suggest further work on BDM biomarkers is warranted.
MAFLD, NAFLD, biomarker, blood DNA methylation, liver fibrosis
2296-858X
Sun, QF
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Tang, LJ
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Wang, MJ
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Zhu, PW
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Li, YY
76fb576c-c4f4-4064-b470-d8c74cecd2eb
Ma, HL
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Huang, OY
153ddc6c-fe51-4fae-9bb4-93c11a5d56a5
Hong, L
a8e1b04a-852f-48e9-b973-8b15d76a0266
Li, G
2c502315-87a2-41b0-91c1-76c6b4c69fec
Byrne, Christopher
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Targher, G
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Liu, WY
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Lu, Y
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Ding, JG
bf676e42-eb9f-4135-9726-ecb23514c14e
Zheng, MH
9d6c3c62-88e9-483c-b186-ddf13b674b4b
Sun, QF
25fa400f-20b8-4336-9dcb-4b4ee46e7412
Tang, LJ
70fbc1df-ea98-4efa-a7c5-4370c936327b
Wang, MJ
2b7c0285-2cab-4edf-8b0c-099a22f0e247
Zhu, PW
747f4d2e-ba65-4cf1-8070-5fb087642463
Li, YY
76fb576c-c4f4-4064-b470-d8c74cecd2eb
Ma, HL
3ac28a1b-af2f-422e-888e-339444db2afe
Huang, OY
153ddc6c-fe51-4fae-9bb4-93c11a5d56a5
Hong, L
a8e1b04a-852f-48e9-b973-8b15d76a0266
Li, G
2c502315-87a2-41b0-91c1-76c6b4c69fec
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Targher, G
5e002803-d2cd-4231-9652-2ad1b8b59dfe
Liu, WY
f634d579-9903-47d3-983a-983b6043c8b8
Lu, Y
c1b26ae2-e58e-4ccf-9b95-2c2fe886fb4b
Ding, JG
bf676e42-eb9f-4135-9726-ecb23514c14e
Zheng, MH
9d6c3c62-88e9-483c-b186-ddf13b674b4b

Sun, QF, Tang, LJ, Wang, MJ, Zhu, PW, Li, YY, Ma, HL, Huang, OY, Hong, L, Li, G, Byrne, Christopher, Targher, G, Liu, WY, Lu, Y, Ding, JG and Zheng, MH (2022) Potential blood DNA methylation biomarker genes for diagnosis of liver fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease. Frontiers in Medicine, 9, [864570]. (doi:10.3389/fmed.2022.864570).

Record type: Article

Abstract

Background and objective: This pilot study aimed to identify potential blood DNA methylation (BDM) biomarker genes for the diagnosis of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: We included a total of 16 NAFLD patients with significant (SLF, liver fibrosis stage ≥ 2) and 16 patients with non-significant liver fibrosis (NSLF, fibrosis stages 0–1). The association between BDM and liver fibrosis was analyzed. Genes were selected based on a stepwise-filtering with CpG islands containing significant differentially methylated probes. Results: The two groups of patients were distinguishable through both t-distributed stochastic neighbor embedding (t-SNE) analysis and unsupervised hierarchical clustering analysis based on their BDM status. BDM levels were significantly higher in the NSLF group than in the SLF group. The methylation levels in the island and shelf regions were also significantly higher in the NSLF group, as well as the methylation levels in the first exon, 3′-untranslated region, body, ExonBnd, non-intergenic region, transcription start site (TSS)1500, and TSS200 regions (all p < 0.05). BDM status was associated with greater histological liver fibrosis, but not with age, sex, or other histological features of NAFLD (p < 0.05). The methylation levels of the hypomethylated CpG island region of CISTR, IFT140, and RGS14 genes were increased in the NSLF group compared to the SLF group (all p < 0.05). Conclusion: BDM may stratify NAFLD patients with significant and non-significant liver fibrosis. The CISTR, IFT140, and RGS14 genes are potential novel candidate BDM biomarkers for liver fibrosis and these pilot data suggest further work on BDM biomarkers is warranted.

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Accepted/In Press date: 22 February 2022
Published date: 31 March 2022
Additional Information: Funding Information: This work was funded by grants from the National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032), and Project of New Century 551 Talent Nurturing in Wenzhou. GT was supported in part by grants from the School of Medicine, University of Verona, Verona, Italy. CB was supported in part by the NIHR Southampton Biomedical Research Centre (IS-BRC-20004), United Kingdom. Publisher Copyright: Copyright © 2022 Sun, Tang, Wang, Zhu, Li, Ma, Huang, Hong, Li, Byrne, Targher, Liu, Lu, Ding and Zheng.
Keywords: MAFLD, NAFLD, biomarker, blood DNA methylation, liver fibrosis

Identifiers

Local EPrints ID: 457918
URI: http://eprints.soton.ac.uk/id/eprint/457918
ISSN: 2296-858X
PURE UUID: 2d88775a-8844-4d0c-bc2e-27461a94e924
ORCID for Christopher Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 22 Jun 2022 16:41
Last modified: 06 Jun 2024 01:38

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Contributors

Author: QF Sun
Author: LJ Tang
Author: MJ Wang
Author: PW Zhu
Author: YY Li
Author: HL Ma
Author: OY Huang
Author: L Hong
Author: G Li
Author: G Targher
Author: WY Liu
Author: Y Lu
Author: JG Ding
Author: MH Zheng

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