Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma
Background: N6-Methyladenosine (m6A) RNA modification is the most prevalent internal modification pattern in eukaryotic mRNAs and plays critical roles in diverse physiological and pathological processes. However, the expression of m6A regulator YTHDF2, its prognostic value, its biological function,...
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Elsevier
2024-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023104129 |
| _version_ | 1827367300257284096 |
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| author | Hang Wang Hui Cai Li Li |
| author_facet | Hang Wang Hui Cai Li Li |
| author_sort | Hang Wang |
| collection | DOAJ |
| description | Background: N6-Methyladenosine (m6A) RNA modification is the most prevalent internal modification pattern in eukaryotic mRNAs and plays critical roles in diverse physiological and pathological processes. However, the expression of m6A regulator YTHDF2, its prognostic value, its biological function, its correlation with tumor microenvironment (TME) immune infiltrates, and related regulatory networks in hepatocellular carcinoma (HCC) remain determined. Methods: TCGA, GTEx, and GEO databases were used to investigate the expression profile of YTHDF2 in HCC. We performed differentially expressed genes (DEGs) analysis and constructed a PPI network to explore the biological processes of YTHDF2 in HCC. Kaplan-Meier curves and Cox regression analysis were used to assess the prognostic value of YTHDF2 and then a clinical prognostic nomogram was constructed. Additionally, ssGSEA was performed to assess the correlation between YTHDF2 and immune infiltration levels. The TISIDB database was applied to explore the expression of YTHDF2 in immune and molecular subtypes of HCC. GSEA identifies the YTHDF2-related signaling pathways. Finally, we utilized miRNet and starBase database to construct regulatory networks for HCC based on lncRNA-miRNA and miRNA-YTHDF2 interactions. Results: YTHDF2 was significantly upregulated in HCC tumor tissues compared with the adjacent normal tissues. HCC patients in the high YTHDF2 expression group had poorer survival. Multivariate Cox analysis suggested that YTHDF2 may be a new independent prognostic indicator for HCC patients, with the prognostic nomogram exhibiting satisfactory results. YTHDF2 expression was significantly correlated with TME immune cell-infiltrating characteristics. Strong correlations were also shown in immune subtypes, molecular subtypes and immune checkpoints. Further analysis revealed that the combination of YTHDF2 expression and immune cell score was considerably associated with survival outcome in HCC patients. GESA analysis demonstrated that high YTHDF2 expression is associated with multiple biological processes and oncogenic pathways. Moreover, 14 possible regulatory networks were constructed, which are associated with HCC progression. Conclusion: Our findings revealed that YTHDF2 may serve as a promising prognostic biomarker for HCC and may regulate the tumor immune microenvironment to provide effective therapeutic strategies. |
| first_indexed | 2024-03-08T09:04:33Z |
| format | Article |
| id | doaj.art-8714ef2f6ac54bae969645c44c1d31a4 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T09:04:33Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8714ef2f6ac54bae969645c44c1d31a42024-02-01T06:31:03ZengElsevierHeliyon2405-84402024-01-01101e23204Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinomaHang Wang0Hui Cai1Li Li2Shengli Clinical Medical College of Fujian Medical University, Department of Health Management, Fujian Provincial Hospital, Fuzhou, Fujian, China; Shengli Clinical Medical College of Fujian Medical University, Department of Disease Prevention and Healthcare, Fujian Provincial Hospital, Fuzhou, Fujian, ChinaShengli Clinical Medical College of Fujian Medical University, Department of Health Management, Fujian Provincial Hospital, Fuzhou, Fujian, ChinaShengli Clinical Medical College of Fujian Medical University, Department of Health Management, Fujian Provincial Hospital, Fuzhou, Fujian, China; Shengli Clinical Medical College of Fujian Medical University, Department of Disease Prevention and Healthcare, Fujian Provincial Hospital, Fuzhou, Fujian, China; Corresponding author. 134 Dong Jie Road, Gulou District, Fuzhou, Fujian, 350001, China.Background: N6-Methyladenosine (m6A) RNA modification is the most prevalent internal modification pattern in eukaryotic mRNAs and plays critical roles in diverse physiological and pathological processes. However, the expression of m6A regulator YTHDF2, its prognostic value, its biological function, its correlation with tumor microenvironment (TME) immune infiltrates, and related regulatory networks in hepatocellular carcinoma (HCC) remain determined. Methods: TCGA, GTEx, and GEO databases were used to investigate the expression profile of YTHDF2 in HCC. We performed differentially expressed genes (DEGs) analysis and constructed a PPI network to explore the biological processes of YTHDF2 in HCC. Kaplan-Meier curves and Cox regression analysis were used to assess the prognostic value of YTHDF2 and then a clinical prognostic nomogram was constructed. Additionally, ssGSEA was performed to assess the correlation between YTHDF2 and immune infiltration levels. The TISIDB database was applied to explore the expression of YTHDF2 in immune and molecular subtypes of HCC. GSEA identifies the YTHDF2-related signaling pathways. Finally, we utilized miRNet and starBase database to construct regulatory networks for HCC based on lncRNA-miRNA and miRNA-YTHDF2 interactions. Results: YTHDF2 was significantly upregulated in HCC tumor tissues compared with the adjacent normal tissues. HCC patients in the high YTHDF2 expression group had poorer survival. Multivariate Cox analysis suggested that YTHDF2 may be a new independent prognostic indicator for HCC patients, with the prognostic nomogram exhibiting satisfactory results. YTHDF2 expression was significantly correlated with TME immune cell-infiltrating characteristics. Strong correlations were also shown in immune subtypes, molecular subtypes and immune checkpoints. Further analysis revealed that the combination of YTHDF2 expression and immune cell score was considerably associated with survival outcome in HCC patients. GESA analysis demonstrated that high YTHDF2 expression is associated with multiple biological processes and oncogenic pathways. Moreover, 14 possible regulatory networks were constructed, which are associated with HCC progression. Conclusion: Our findings revealed that YTHDF2 may serve as a promising prognostic biomarker for HCC and may regulate the tumor immune microenvironment to provide effective therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S2405844023104129m6A methylationHepatocellular carcinomaPrognostic signatureImmune infiltrationEpitranscriptomics |
| spellingShingle | Hang Wang Hui Cai Li Li Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma Heliyon m6A methylation Hepatocellular carcinoma Prognostic signature Immune infiltration Epitranscriptomics |
| title | Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma |
| title_full | Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma |
| title_fullStr | Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma |
| title_full_unstemmed | Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma |
| title_short | Comprehensive analysis of m6A reader YTHDF2 prognosis, immune infiltration, and related regulatory networks in hepatocellular carcinoma |
| title_sort | comprehensive analysis of m6a reader ythdf2 prognosis immune infiltration and related regulatory networks in hepatocellular carcinoma |
| topic | m6A methylation Hepatocellular carcinoma Prognostic signature Immune infiltration Epitranscriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023104129 |
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