GNA15 predicts poor outcomes as a novel biomarker related to M2 macrophage infiltration in ovarian cancer.

IF 5.7 2区 医学 Q1 IMMUNOLOGY
Frontiers in Immunology Pub Date : 2025-02-07 eCollection Date: 2025-01-01 DOI:10.3389/fimmu.2025.1512086
Qin Liu, Yabing Sun, Tao Zhang, Wanrun Lin, Jing Zhang, Huijuan Zhang, Wenxin Zheng, Hong Xu, Feng Zhou
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引用次数: 0

Abstract

Background: The 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.

Methods: Prognostic 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.

Results: Gene 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.

Conclusion: GNA15 plays an immunosuppressive role in OC progression linked to M2-like TAMs polarization and stands as a potential prognostic marker in OC.

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来源期刊
CiteScore
9.80
自引率
11.00%
发文量
7153
审稿时长
14 weeks
期刊介绍: Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.
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