GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer
BackgroundThe exploration of genetic signatures within the ovarian cancer (OC) tumor microenvironment (TME) remains limited. M2-like tumor-associated macrophages (M2-like TAMs) are pivotal in OC progression and therapy. This study aims to establish a novel prognostic signature and identify M2-like T...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1512086/full |
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| author | Qin Liu Qin Liu Yabing Sun Yabing Sun Tao Zhang Wanrun Lin Jing Zhang Huijuan Zhang Huijuan Zhang Wenxin Zheng Hong Xu Hong Xu Feng Zhou Feng Zhou |
| author_facet | Qin Liu Qin Liu Yabing Sun Yabing Sun Tao Zhang Wanrun Lin Jing Zhang Huijuan Zhang Huijuan Zhang Wenxin Zheng Hong Xu Hong Xu Feng Zhou Feng Zhou |
| author_sort | Qin Liu |
| collection | DOAJ |
| description | BackgroundThe exploration of genetic signatures within the ovarian cancer (OC) tumor microenvironment (TME) remains limited. M2-like tumor-associated macrophages (M2-like TAMs) are pivotal in OC progression and therapy. This study aims to establish a novel prognostic signature and identify M2-like TAM-related biomarkers in OC using RNAseq-based transcriptome analysis.MethodsPrognostic M2-like TAM-related genes were identified through univariate Cox regression, consensus clustering, and LASSO regression. Immune landscape analysis was conducted to assess immune cell composition and immune checkpoint genes in high- and low-risk groups. Subsequently, in vitro cell experiments and OC cohorts were performed.ResultsGene set enrichment analysis revealed that GNA15 is involved in immune responses like leukocyte transendothelial migration and FcγR-mediated phagocytosis. GNA15 was up-regulated in cisplatin-resistant OC cells, and its in vitro down-regulation decreased cell proliferation. An eight-gene prognostic model, including M2-like TAM-related genes, independently predicted poor outcomes in OC. GNA15 emerged as a hub gene positively correlated with M2-like TAMs infiltration, predicting unfavorable outcomes across OC cohorts. Moreover, GNA15 expression correlated positively with CD163 expression, suggesting its role in macrophage polarization.ConclusionGNA15 plays an immunosuppressive role in OC progression linked to M2-like TAMs polarization and stands as a potential prognostic marker in OC. |
| format | Article |
| id | doaj-art-d2b50dc9c1ba4176a4b940c4986ba2ab |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-d2b50dc9c1ba4176a4b940c4986ba2ab2025-02-07T05:10:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15120861512086GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancerQin Liu0Qin Liu1Yabing Sun2Yabing Sun3Tao Zhang4Wanrun Lin5Jing Zhang6Huijuan Zhang7Huijuan Zhang8Wenxin Zheng9Hong Xu10Hong Xu11Feng Zhou12Feng Zhou13Department of Pathology, The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pathology, Zhejiang University School of Medicine Women’s Hospital, Hangzhou, Zhejiang, ChinaDepartment of Gynecology, The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Diseases, Shanghai, ChinaDepartment of Gynecology, Zhejiang University School of Medicine Women’s Hospital, Hangzhou, Zhejiang, ChinaLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesDepartment of Biological Sciences, College of Arts and Sciences, University at Albany, State University of New York (SUNY), Albany, NY, United StatesDepartment of Pathology, The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Diseases, Shanghai, ChinaDepartment of Pathology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Gynecology, The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Diseases, Shanghai, ChinaDepartment of Pathology, The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of Embryo Original Diseases, Shanghai, ChinaBackgroundThe exploration of genetic signatures within the ovarian cancer (OC) tumor microenvironment (TME) remains limited. M2-like tumor-associated macrophages (M2-like TAMs) are pivotal in OC progression and therapy. This study aims to establish a novel prognostic signature and identify M2-like TAM-related biomarkers in OC using RNAseq-based transcriptome analysis.MethodsPrognostic M2-like TAM-related genes were identified through univariate Cox regression, consensus clustering, and LASSO regression. Immune landscape analysis was conducted to assess immune cell composition and immune checkpoint genes in high- and low-risk groups. Subsequently, in vitro cell experiments and OC cohorts were performed.ResultsGene set enrichment analysis revealed that GNA15 is involved in immune responses like leukocyte transendothelial migration and FcγR-mediated phagocytosis. GNA15 was up-regulated in cisplatin-resistant OC cells, and its in vitro down-regulation decreased cell proliferation. An eight-gene prognostic model, including M2-like TAM-related genes, independently predicted poor outcomes in OC. GNA15 emerged as a hub gene positively correlated with M2-like TAMs infiltration, predicting unfavorable outcomes across OC cohorts. Moreover, GNA15 expression correlated positively with CD163 expression, suggesting its role in macrophage polarization.ConclusionGNA15 plays an immunosuppressive role in OC progression linked to M2-like TAMs polarization and stands as a potential prognostic marker in OC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1512086/fullovarian carcinomacancer microenvironmenttumor-associated macrophagesprognostic modelGNA15 |
| spellingShingle | Qin Liu Qin Liu Yabing Sun Yabing Sun Tao Zhang Wanrun Lin Jing Zhang Huijuan Zhang Huijuan Zhang Wenxin Zheng Hong Xu Hong Xu Feng Zhou Feng Zhou GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer Frontiers in Immunology ovarian carcinoma cancer microenvironment tumor-associated macrophages prognostic model GNA15 |
| title | GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer |
| title_full | GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer |
| title_fullStr | GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer |
| title_full_unstemmed | GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer |
| title_short | GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer |
| title_sort | gna15 predicts poor outcomes as a novel biomarker related to m2 macrophage infiltration in ovarian cancer |
| topic | ovarian carcinoma cancer microenvironment tumor-associated macrophages prognostic model GNA15 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1512086/full |
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