Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma
Background and aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, characterized by aggressive behavior, limited therapeutic efficacy, and poor patient outcomes. TPX2, a microtubule-associated protein essential for mitotic spindle formation, has been associ...
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Elsevier
2025-09-01
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| author | Hui Peng Yong-peng Wei Xin-bo Liu Yu Wang Jian-yong Yuan |
| author_facet | Hui Peng Yong-peng Wei Xin-bo Liu Yu Wang Jian-yong Yuan |
| author_sort | Hui Peng |
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| description | Background and aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, characterized by aggressive behavior, limited therapeutic efficacy, and poor patient outcomes. TPX2, a microtubule-associated protein essential for mitotic spindle formation, has been associated with tumorigenesis in various cancers. However, its functional significance in shaping the immune landscape and influencing treatment sensitivity in HCC remains insufficiently elucidated. Methods: We conducted an integrated multi-omics analysis using transcriptomic (TCGA, GTEx, GEO), proteomic (CPTAC), and pharmacogenomic (GDSC, PRISM, CTRP) datasets to assess TPX2 expression patterns in HCC. We performed differential expression analysis, survival analysis, Cox regression, and nomogram construction. Co-expression modules were identified via weighted gene co-expression network analysis (WGCNA), followed by GO and KEGG enrichment analyses. The correlations between TPX2 expression levels and immune and genomic features were examined, and drug sensitivity associations were evaluated. Results: TPX2 was consistently overexpressed in HCC tissues and associated with advanced tumor stage, higher grade, and poor survival. WGCNA revealed TPX2-enriched modules linked to cell cycle and DNA replication pathways. High TPX2 expression levels were correlated with immunosuppressive features, including reduced lymphocyte infiltration, lower IFN-γ response, and increased expression levels of immune checkpoint molecules (PD-1, CTLA-4, HAVCR2). TPX2-high tumors also exhibited greater genomic instability. Drug sensitivity analysis indicated resistance to several chemotherapeutics, but increased sensitivity to mitotic inhibitors and targeted agents. Conclusions: TPX2 is a key driver of proliferation and immune evasion in HCC, potentially serving as a diagnostic and prognostic biomarker to guide treatment strategies involving mitotic- or immune-based therapies. |
| format | Article |
| id | doaj-art-04c117fadd244b279fdc1c84d6414b47 |
| institution | Kabale University |
| issn | 2772-9478 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iLIVER |
| spelling | doaj-art-04c117fadd244b279fdc1c84d6414b472025-08-25T04:14:56ZengElsevieriLIVER2772-94782025-09-014310018410.1016/j.iliver.2025.100184Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinomaHui Peng0Yong-peng Wei1Xin-bo Liu2Yu Wang3Jian-yong Yuan4Department of General Surgery, Xiangxi Tujia and Miao Autonomous Prefecture Ethnic Traditional Chinese Medicine Hospital, Xiangxi Tujia and Miao Autonomous Prefecture 416000, Hunan, ChinaDepartment of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaDepartment of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, China; Corresponding authors.Department of Hepatobiliary Pancreatic Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Corresponding authors.Background and aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, characterized by aggressive behavior, limited therapeutic efficacy, and poor patient outcomes. TPX2, a microtubule-associated protein essential for mitotic spindle formation, has been associated with tumorigenesis in various cancers. However, its functional significance in shaping the immune landscape and influencing treatment sensitivity in HCC remains insufficiently elucidated. Methods: We conducted an integrated multi-omics analysis using transcriptomic (TCGA, GTEx, GEO), proteomic (CPTAC), and pharmacogenomic (GDSC, PRISM, CTRP) datasets to assess TPX2 expression patterns in HCC. We performed differential expression analysis, survival analysis, Cox regression, and nomogram construction. Co-expression modules were identified via weighted gene co-expression network analysis (WGCNA), followed by GO and KEGG enrichment analyses. The correlations between TPX2 expression levels and immune and genomic features were examined, and drug sensitivity associations were evaluated. Results: TPX2 was consistently overexpressed in HCC tissues and associated with advanced tumor stage, higher grade, and poor survival. WGCNA revealed TPX2-enriched modules linked to cell cycle and DNA replication pathways. High TPX2 expression levels were correlated with immunosuppressive features, including reduced lymphocyte infiltration, lower IFN-γ response, and increased expression levels of immune checkpoint molecules (PD-1, CTLA-4, HAVCR2). TPX2-high tumors also exhibited greater genomic instability. Drug sensitivity analysis indicated resistance to several chemotherapeutics, but increased sensitivity to mitotic inhibitors and targeted agents. Conclusions: TPX2 is a key driver of proliferation and immune evasion in HCC, potentially serving as a diagnostic and prognostic biomarker to guide treatment strategies involving mitotic- or immune-based therapies.http://www.sciencedirect.com/science/article/pii/S2772947825000428Hepatocellular carcinomaTPX2Immune evasionBiomarker |
| spellingShingle | Hui Peng Yong-peng Wei Xin-bo Liu Yu Wang Jian-yong Yuan Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma iLIVER Hepatocellular carcinoma TPX2 Immune evasion Biomarker |
| title | Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma |
| title_full | Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma |
| title_fullStr | Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma |
| title_full_unstemmed | Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma |
| title_short | Integrated multi-omics analysis identifies TPX2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma |
| title_sort | integrated multi omics analysis identifies tpx2 as a potential prognostic and immunological biomarker in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma TPX2 Immune evasion Biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2772947825000428 |
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