Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis
Hepatitis B virus (HBV) infection remains the leading cause of liver fibrosis (LF) worldwide, especially in China. Identification of decisive diagnostic biomarkers for HBV-associated liver fibrosis (HBV-LF) is required to prevent chronic hepatitis B (CHB) from progressing to liver cancer and to more...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1010160/full |
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| author | Mengqin Yuan Xue Hu Lichao Yao Pingji Liu Yingan Jiang Lanjuan Li Lanjuan Li |
| author_facet | Mengqin Yuan Xue Hu Lichao Yao Pingji Liu Yingan Jiang Lanjuan Li Lanjuan Li |
| author_sort | Mengqin Yuan |
| collection | DOAJ |
| description | Hepatitis B virus (HBV) infection remains the leading cause of liver fibrosis (LF) worldwide, especially in China. Identification of decisive diagnostic biomarkers for HBV-associated liver fibrosis (HBV-LF) is required to prevent chronic hepatitis B (CHB) from progressing to liver cancer and to more effectively select the best treatment strategy. We obtained 43 samples from CHB patients without LF and 81 samples from CHB patients with LF (GSE84044 dataset). Among these, 173 differentially expressed genes (DEGs) were identified. Functional analysis revealed that these DEGs predominantly participated in immune-, extracellular matrix-, and metabolism-related processes. Subsequently, we integrated four algorithms (LASSO regression, SVM-RFE, RF, and WGCNA) to determine diagnostic biomarkers for HBV-LF. These analyses and receive operating characteristic curves identified the genes for phosphatidic acid phosphatase type 2C (PPAP2C) and versican (VCAN) as potentially valuable diagnostic biomarkers for HBV-LF. Single-sample gene set enrichment analysis (ssGSEA) further confirmed the immune landscape of HBV-LF. The two diagnostic biomarkers also significantly correlated with infiltrating immune cells. The potential regulatory mechanisms of VCAN underlying the occurrence and development of HBV-LF were also analyzed. These collective findings implicate VCAN as a novel diagnostic biomarker for HBV-LF, and infiltration of immune cells may critically contribute to the occurrence and development of HBV-LF. |
| first_indexed | 2024-04-12T09:35:22Z |
| format | Article |
| id | doaj.art-2d8744ab041e4b33883efe12598a6aeb |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-12T09:35:22Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-2d8744ab041e4b33883efe12598a6aeb2022-12-22T03:38:15ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-10-01910.3389/fmolb.2022.10101601010160Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosisMengqin Yuan0Xue Hu1Lichao Yao2Pingji Liu3Yingan Jiang4Lanjuan Li5Lanjuan Li6Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaDepartment of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, ChinaHepatitis B virus (HBV) infection remains the leading cause of liver fibrosis (LF) worldwide, especially in China. Identification of decisive diagnostic biomarkers for HBV-associated liver fibrosis (HBV-LF) is required to prevent chronic hepatitis B (CHB) from progressing to liver cancer and to more effectively select the best treatment strategy. We obtained 43 samples from CHB patients without LF and 81 samples from CHB patients with LF (GSE84044 dataset). Among these, 173 differentially expressed genes (DEGs) were identified. Functional analysis revealed that these DEGs predominantly participated in immune-, extracellular matrix-, and metabolism-related processes. Subsequently, we integrated four algorithms (LASSO regression, SVM-RFE, RF, and WGCNA) to determine diagnostic biomarkers for HBV-LF. These analyses and receive operating characteristic curves identified the genes for phosphatidic acid phosphatase type 2C (PPAP2C) and versican (VCAN) as potentially valuable diagnostic biomarkers for HBV-LF. Single-sample gene set enrichment analysis (ssGSEA) further confirmed the immune landscape of HBV-LF. The two diagnostic biomarkers also significantly correlated with infiltrating immune cells. The potential regulatory mechanisms of VCAN underlying the occurrence and development of HBV-LF were also analyzed. These collective findings implicate VCAN as a novel diagnostic biomarker for HBV-LF, and infiltration of immune cells may critically contribute to the occurrence and development of HBV-LF.https://www.frontiersin.org/articles/10.3389/fmolb.2022.1010160/fullhepatitis B virus-related liver fibrosisdiagnostic biomarkerbioinformatic analysismachine-learning strategiesimmune cell infiltration |
| spellingShingle | Mengqin Yuan Xue Hu Lichao Yao Pingji Liu Yingan Jiang Lanjuan Li Lanjuan Li Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis Frontiers in Molecular Biosciences hepatitis B virus-related liver fibrosis diagnostic biomarker bioinformatic analysis machine-learning strategies immune cell infiltration |
| title | Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis |
| title_full | Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis |
| title_fullStr | Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis |
| title_full_unstemmed | Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis |
| title_short | Comprehensive bioinformatics and machine learning analysis identify VCAN as a novel biomarker of hepatitis B virus-related liver fibrosis |
| title_sort | comprehensive bioinformatics and machine learning analysis identify vcan as a novel biomarker of hepatitis b virus related liver fibrosis |
| topic | hepatitis B virus-related liver fibrosis diagnostic biomarker bioinformatic analysis machine-learning strategies immune cell infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.1010160/full |
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