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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1565924
Pan-Cancer Analysis of Phagocytosis Regulators in Female-Specific Cancers: A Focus on HMGB2
Provisionally accepted- Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment, regulating immune escape and promoting cancer progression. Understanding the role of phagocytosis regulators in female-specific cancers is essential for developing effective therapeutic strategies.We performed comprehensive analyses of public databases to evaluate the expression, somatic mutations, and copy number variations of phagocytosis regulators. DNA methylation patterns, biological pathways, survival outcomes, and drug sensitivity were assessed. Additionally, immune modulators, immune cell infiltration, and single-cell sequencing were used to explore alterations in phagocytosis and their cellular origins. The functional role of HMGB2 in tumor cell behavior was validated through in vitro assays.Phagocytosis regulators exhibited differential expression across various female-specific cancers, with key genes such as CD47 and FOXO1 playing significant roles in modulating tumor progression. High-frequency mutations were found in PTEN, ARID1A, and UBR4. Genes like COX5B and MS4A1 emerged as potential predictors of clinical outcomes and therapeutic response. HMGB2 knockdown significantly inhibited cancer cell proliferation, migration, and invasion in femalespecific cancers. HMGB2 knockdown in macrophages led to a significant impairment in phagocytosis of breast, cervical, ovarian, and endometrial cancer cells. Furthermore, when HMGB2 knockdown was combined with Palbociclib treatment, a significant decrease in tumor cell proliferation was observed across multiple cancer models.This study highlights the pivotal role of phagocytosis regulators, particularly HMGB2, in the progression of female-specific cancers. Targeting HMGB2 offers promising therapeutic opportunities, potentially enhancing precision oncology and improving patient outcomes.
Keywords: phagocytosis regulators, HMGB2, Female-specific cancers, Tumor Microenvironment, Cancer proliferation and invasion, therapeutic targets
Received: 23 Jan 2025; Accepted: 09 Apr 2025.
Copyright: © 2025 Lu, Ren, Zhao, Li, Wang and Zhang. 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: Xiaoqin Lu, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 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.