Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease
Background and objectiveThis 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).MethodsWe included a total of 16 NAFLD patients with significant (SLF, liver fibrosis stage ≥ 2) and 16 pa...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.864570/full |
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| author | Qing-Feng Sun Liang-Jie Tang Ming-Jie Wang Pei-Wu Zhu Yang-Yang Li Hong-Lei Ma Hong-Lei Ma Ou-Yang Huang Liang Hong Gang Li Christopher D. Byrne Giovanni Targher Wen-Yue Liu Yan Lu Ji-Guang Ding Ming-Hua Zheng Ming-Hua Zheng Ming-Hua Zheng |
| author_facet | Qing-Feng Sun Liang-Jie Tang Ming-Jie Wang Pei-Wu Zhu Yang-Yang Li Hong-Lei Ma Hong-Lei Ma Ou-Yang Huang Liang Hong Gang Li Christopher D. Byrne Giovanni Targher Wen-Yue Liu Yan Lu Ji-Guang Ding Ming-Hua Zheng Ming-Hua Zheng Ming-Hua Zheng |
| author_sort | Qing-Feng Sun |
| collection | DOAJ |
| description | Background and objectiveThis 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).MethodsWe 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.ResultsThe 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).ConclusionBDM 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. |
| first_indexed | 2024-12-13T01:29:16Z |
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| id | doaj.art-4257ed3e22b44356847d75b6ecb45bce |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-13T01:29:16Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-4257ed3e22b44356847d75b6ecb45bce2022-12-22T00:04:02ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-03-01910.3389/fmed.2022.864570864570Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver DiseaseQing-Feng Sun0Liang-Jie Tang1Ming-Jie Wang2Pei-Wu Zhu3Yang-Yang Li4Hong-Lei Ma5Hong-Lei Ma6Ou-Yang Huang7Liang Hong8Gang Li9Christopher D. Byrne10Giovanni Targher11Wen-Yue Liu12Yan Lu13Ji-Guang Ding14Ming-Hua Zheng15Ming-Hua Zheng16Ming-Hua Zheng17Department of Infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaNAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaNAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of General Practice, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, ChinaNAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaNAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaNational Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, United KingdomSection of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Verona, University of Verona, Verona, ItalyDepartment of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China0Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Infectious Diseases, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaNAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China1Institute of Hepatology, Wenzhou Medical University, Wenzhou, China2Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, ChinaBackground and objectiveThis 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).MethodsWe 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.ResultsThe 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).ConclusionBDM 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.https://www.frontiersin.org/articles/10.3389/fmed.2022.864570/fullNAFLDliver fibrosisblood DNA methylationbiomarkerMAFLD |
| spellingShingle | Qing-Feng Sun Liang-Jie Tang Ming-Jie Wang Pei-Wu Zhu Yang-Yang Li Hong-Lei Ma Hong-Lei Ma Ou-Yang Huang Liang Hong Gang Li Christopher D. Byrne Giovanni Targher Wen-Yue Liu Yan Lu Ji-Guang Ding Ming-Hua Zheng Ming-Hua Zheng Ming-Hua Zheng Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease Frontiers in Medicine NAFLD liver fibrosis blood DNA methylation biomarker MAFLD |
| title | Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease |
| title_full | Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease |
| title_fullStr | Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease |
| title_full_unstemmed | Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease |
| title_short | Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease |
| title_sort | potential blood dna methylation biomarker genes for diagnosis of liver fibrosis in patients with biopsy proven non alcoholic fatty liver disease |
| topic | NAFLD liver fibrosis blood DNA methylation biomarker MAFLD |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.864570/full |
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