Guangyi Zhu, Shijian Li, Ziyang Luo, Ning Wen, Haibin Li, Yang Fu, Weixuan Li, Jihua Wu, Xuyong Sun
{"title":"基于生物信息学分析探索肝移植术后肝癌复发的生物标志物。","authors":"Guangyi Zhu, Shijian Li, Ziyang Luo, Ning Wen, Haibin Li, Yang Fu, Weixuan Li, Jihua Wu, Xuyong Sun","doi":"10.1007/s10528-025-11227-8","DOIUrl":null,"url":null,"abstract":"<p><p>This study aimed to explore thrombin-related prognostic biomarkers for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Bioinformatics analyses were conducted using TCGA-LIHC and GEO datasets. LASSO Cox regression screened thrombin-related genes (TRGs). Differential expression analysis, GSEA, and protein-protein interaction (PPI) network analysis were performed to identify key pathways and hub genes. Clinical validation included immunohistochemistry (IHC) on 78 post-LT HCC tissues. In vitro assays (CCK-8, Transwell, Colony formation) assessed MMP1/SPP1 roles in HCC cell proliferation and migration. Nine TRGs were prognostic in HCC, with MMP1 and SPP1 emerging as core regulators linked to EMT. Both genes were significantly upregulated in recurrent HCC tissues (1-year recurrence group vs. non-recurrence, P < 0.05) and correlated with reduced overall survival (OS) and recurrence-free survival (RFS). GSEA revealed EMT as a key enriched pathway. PPI network analysis highlighted MMP1/SPP1 centrality in ECM remodeling and cell adhesion. Clinical samples confirmed MMP1 association with vascular invasion (P = 0.023) and poor differentiation. In vitro, MMP1/SPP1 overexpression enhanced HCC cell proliferation, migration, and colony formation. Multivariate analysis identified MMP1 expression and tumor differentiation as independent recurrence risk factors. MMP1 and SPP1 are potential biomarkers for predicting post-LT HCC recurrence, likely driving metastasis via EMT activation. Their overexpression correlates with aggressive tumor behavior and adverse outcomes, offering prognostic utility and therapeutic targets to improve transplant outcomes.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploration Biomarkers for Recurrence of Hepatocellular Carcinoma After Liver Transplantation Based on Bioinformatics Analysis.\",\"authors\":\"Guangyi Zhu, Shijian Li, Ziyang Luo, Ning Wen, Haibin Li, Yang Fu, Weixuan Li, Jihua Wu, Xuyong Sun\",\"doi\":\"10.1007/s10528-025-11227-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>This study aimed to explore thrombin-related prognostic biomarkers for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Bioinformatics analyses were conducted using TCGA-LIHC and GEO datasets. LASSO Cox regression screened thrombin-related genes (TRGs). Differential expression analysis, GSEA, and protein-protein interaction (PPI) network analysis were performed to identify key pathways and hub genes. Clinical validation included immunohistochemistry (IHC) on 78 post-LT HCC tissues. In vitro assays (CCK-8, Transwell, Colony formation) assessed MMP1/SPP1 roles in HCC cell proliferation and migration. Nine TRGs were prognostic in HCC, with MMP1 and SPP1 emerging as core regulators linked to EMT. Both genes were significantly upregulated in recurrent HCC tissues (1-year recurrence group vs. non-recurrence, P < 0.05) and correlated with reduced overall survival (OS) and recurrence-free survival (RFS). GSEA revealed EMT as a key enriched pathway. PPI network analysis highlighted MMP1/SPP1 centrality in ECM remodeling and cell adhesion. Clinical samples confirmed MMP1 association with vascular invasion (P = 0.023) and poor differentiation. In vitro, MMP1/SPP1 overexpression enhanced HCC cell proliferation, migration, and colony formation. Multivariate analysis identified MMP1 expression and tumor differentiation as independent recurrence risk factors. MMP1 and SPP1 are potential biomarkers for predicting post-LT HCC recurrence, likely driving metastasis via EMT activation. 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Exploration Biomarkers for Recurrence of Hepatocellular Carcinoma After Liver Transplantation Based on Bioinformatics Analysis.
This study aimed to explore thrombin-related prognostic biomarkers for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Bioinformatics analyses were conducted using TCGA-LIHC and GEO datasets. LASSO Cox regression screened thrombin-related genes (TRGs). Differential expression analysis, GSEA, and protein-protein interaction (PPI) network analysis were performed to identify key pathways and hub genes. Clinical validation included immunohistochemistry (IHC) on 78 post-LT HCC tissues. In vitro assays (CCK-8, Transwell, Colony formation) assessed MMP1/SPP1 roles in HCC cell proliferation and migration. Nine TRGs were prognostic in HCC, with MMP1 and SPP1 emerging as core regulators linked to EMT. Both genes were significantly upregulated in recurrent HCC tissues (1-year recurrence group vs. non-recurrence, P < 0.05) and correlated with reduced overall survival (OS) and recurrence-free survival (RFS). GSEA revealed EMT as a key enriched pathway. PPI network analysis highlighted MMP1/SPP1 centrality in ECM remodeling and cell adhesion. Clinical samples confirmed MMP1 association with vascular invasion (P = 0.023) and poor differentiation. In vitro, MMP1/SPP1 overexpression enhanced HCC cell proliferation, migration, and colony formation. Multivariate analysis identified MMP1 expression and tumor differentiation as independent recurrence risk factors. MMP1 and SPP1 are potential biomarkers for predicting post-LT HCC recurrence, likely driving metastasis via EMT activation. Their overexpression correlates with aggressive tumor behavior and adverse outcomes, offering prognostic utility and therapeutic targets to improve transplant outcomes.
期刊介绍：
Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses.
Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication.
Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses.
Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods.
Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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