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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1512086
This article is part of the Research Topic Immunological Aspects and Immunotherapy in Gynecologic Cancers View all articles

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

Provisionally accepted
Qin Liu Qin Liu 1Yabing Sun Yabing Sun 1Wanrun Lin Wanrun Lin 2Jing Zhang Jing Zhang 3Huijuan Zhang Huijuan Zhang 1Wenxin Zheng Wenxin Zheng 4Hong Xu Hong Xu 1Feng Zhou Feng Zhou 1*
  • 1 The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • 2 National Institutes of Health (NIH), Bethesda, Maryland, United States
  • 3 College of Arts and Sciences, University at Albany, New york, United States
  • 4 University of Texas Southwestern Medical Center, Dallas, Texas, United States

The final, formatted version of the article will be published soon.

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

    Keywords: ovarian carcinoma, Cancer microenvironment, Tumor-associated macrophages, Prognostic model, GNA15

    Received: 16 Oct 2024; Accepted: 21 Jan 2025.

    Copyright: © 2025 Liu, Sun, Lin, Zhang, Zhang, Zheng, Xu and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Feng Zhou, The International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.