Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancer
BackgroundHMGA2, as a transcription factor, facilitates oncogenesis and malignant progression by coordinating cell cycle dysregulation, compromising DNA repair machinery, and suppressing cancer cell apoptosis. However, its roles in prognostication and tumor immune microenvironment modulation in endo...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559278/full |
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| author | Peng Jiang Jiaxin Yu Yunfeng Zheng Chenfan Tian Yuan Tu Chunxia Gong Hangkun Yu Yi Luo Zhuoying Hu |
| author_facet | Peng Jiang Jiaxin Yu Yunfeng Zheng Chenfan Tian Yuan Tu Chunxia Gong Hangkun Yu Yi Luo Zhuoying Hu |
| author_sort | Peng Jiang |
| collection | DOAJ |
| description | BackgroundHMGA2, as a transcription factor, facilitates oncogenesis and malignant progression by coordinating cell cycle dysregulation, compromising DNA repair machinery, and suppressing cancer cell apoptosis. However, its roles in prognostication and tumor immune microenvironment modulation in endometrial cancer (EC) remain incompletely defined.MethodsWe systematically analyzed HMGA2 expression patterns and clinical prognostic value in EC using bioinformatics strategies, including TCGA and GTEX data mining, as well as single gene expression analysis. Functional enrichment analysis (GSEA and KEGG) identified HMGA2-associated pathways. The correlation between HMGA2 and immune infiltration was assessed via TIMER and TISIDB. Subsequent in vitro (proliferation, migration, colony formation) and in vivo (xenograft models) experimental were used to validate HMGA2’s role in promoting EC progression. The correlation between HMGA2 and macrophage markers (CD86 and CD206) was validated through clinical tissue samples by IHC. Finally, a recurrence-predictive nomogram incorporating HMGA2 with clinicopathological parameters was established.ResultsHMGA2 exhibited significant upregulation in endometrial cancer (EC) tissues and correlated with poor patient prognosis. Immunoassay showed that high expression of HMGA2 was negatively correlated with infiltration of various immune cells, especially M1 macrophages. Cytological experiments showed that knocking down HMGA2 significantly inhibited EC cell proliferation, migration, invasion, and drug resistance, while overexpression of HMGA2 promoted the above phenotype; Animal experiments showed that knocking down HMGA2 significantly inhibited the growth of EC tumors and the expression of M1 macrophage marker CD86. The combination of HMGA2 inhibitors and targeted macrophage immunotherapy (CD47 monoclonal antibody) had the better tumor suppression effect. Clinical sample analysis found that high expression of HMGA2 was significantly negatively correlated with CD86 and positively correlated with CD206 expression. Patients with low HMGA2 expression showed enhanced immune therapy responsiveness. The nomogram model based on HMGA2 and clinical pathological parameters showed better predictive performance (AUC=0.855, sensitivity=79.0%, specificity=76.8%).ConclusionHMGA2 is a potential diagnostic and prognostic biomarker for the EC. HMGA2 may drive the occurrence and development of EC by inhibiting the infiltration of immune cells, especially M1 macrophages. Therapeutic targeting of HMGA2 is a novel strategy for EC intervention. |
| format | Article |
| id | doaj-art-934f53eddab6443b8be5ec7939221bf8 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-934f53eddab6443b8be5ec7939221bf82025-08-20T02:41:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15592781559278Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancerPeng Jiang0Jiaxin Yu1Yunfeng Zheng2Chenfan Tian3Yuan Tu4Chunxia Gong5Hangkun Yu6Yi Luo7Zhuoying Hu8Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaBackgroundHMGA2, as a transcription factor, facilitates oncogenesis and malignant progression by coordinating cell cycle dysregulation, compromising DNA repair machinery, and suppressing cancer cell apoptosis. However, its roles in prognostication and tumor immune microenvironment modulation in endometrial cancer (EC) remain incompletely defined.MethodsWe systematically analyzed HMGA2 expression patterns and clinical prognostic value in EC using bioinformatics strategies, including TCGA and GTEX data mining, as well as single gene expression analysis. Functional enrichment analysis (GSEA and KEGG) identified HMGA2-associated pathways. The correlation between HMGA2 and immune infiltration was assessed via TIMER and TISIDB. Subsequent in vitro (proliferation, migration, colony formation) and in vivo (xenograft models) experimental were used to validate HMGA2’s role in promoting EC progression. The correlation between HMGA2 and macrophage markers (CD86 and CD206) was validated through clinical tissue samples by IHC. Finally, a recurrence-predictive nomogram incorporating HMGA2 with clinicopathological parameters was established.ResultsHMGA2 exhibited significant upregulation in endometrial cancer (EC) tissues and correlated with poor patient prognosis. Immunoassay showed that high expression of HMGA2 was negatively correlated with infiltration of various immune cells, especially M1 macrophages. Cytological experiments showed that knocking down HMGA2 significantly inhibited EC cell proliferation, migration, invasion, and drug resistance, while overexpression of HMGA2 promoted the above phenotype; Animal experiments showed that knocking down HMGA2 significantly inhibited the growth of EC tumors and the expression of M1 macrophage marker CD86. The combination of HMGA2 inhibitors and targeted macrophage immunotherapy (CD47 monoclonal antibody) had the better tumor suppression effect. Clinical sample analysis found that high expression of HMGA2 was significantly negatively correlated with CD86 and positively correlated with CD206 expression. Patients with low HMGA2 expression showed enhanced immune therapy responsiveness. The nomogram model based on HMGA2 and clinical pathological parameters showed better predictive performance (AUC=0.855, sensitivity=79.0%, specificity=76.8%).ConclusionHMGA2 is a potential diagnostic and prognostic biomarker for the EC. HMGA2 may drive the occurrence and development of EC by inhibiting the infiltration of immune cells, especially M1 macrophages. Therapeutic targeting of HMGA2 is a novel strategy for EC intervention.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559278/fullendometrial cancerHMGA2immuneprognostic valuemacropha ge polarization |
| spellingShingle | Peng Jiang Jiaxin Yu Yunfeng Zheng Chenfan Tian Yuan Tu Chunxia Gong Hangkun Yu Yi Luo Zhuoying Hu Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancer Frontiers in Immunology endometrial cancer HMGA2 immune prognostic value macropha ge polarization |
| title | Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancer |
| title_full | Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancer |
| title_fullStr | Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancer |
| title_full_unstemmed | Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancer |
| title_short | Prognostic significance and immune infiltration analysis of HMGA2 in endometrial cancer |
| title_sort | prognostic significance and immune infiltration analysis of hmga2 in endometrial cancer |
| topic | endometrial cancer HMGA2 immune prognostic value macropha ge polarization |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559278/full |
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