Yan Xuejun, Li Rongnian, Xu Jing, Liu Hua, He Minmin, Jiang Xingjun, Ren Caiping, Zhou Quanwei
NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.
Xiangtan Hospital of Traditional Chinese Medicine, Xiangtan, Hunan, China.
Cancer Immunol Immunother. 2025 May 15;74(7):204. doi: 10.1007/s00262-025-04063-7.
Glioma, a prevalent malignant intracranial tumor, exhibits limited therapeutic efficacy due to its immunosuppressive microenvironment, leading to a poor prognosis for patients. ARHGDIB is implicated in the remodeling of the tumor microenvironment and plays a significant role in the pathogenesis of various tumors. However, its regulatory effect within the immune microenvironment of glioma remains unclear.
The mRNA expression pattern of ARHGDIB was analyzed using public databases, and its expression was further validated in our collected cohort through quantitative PCR (qPCR) and immunohistochemistry (IHC). Kaplan-Meier survival analysis and LASSO-Cox regression were employed to ascertain the clinical significance of ARHGDIB in glioma. Subsequently, we systematically evaluated the association between ARHGDIB expression and immune characteristics within the glioma microenvironment, as well as its potential to predict treatment response in glioma. Additionally, in vitro experiments were conducted to elucidate the role of ARHGDIB in remodeling the glioma microenvironment and promoting tumor malignancy progression.
Combined with bioinformatics analysis of public databases and validation with qPCR and IHC on our cohort, our findings indicate that ARHGDIB is markedly overexpressed in glioma and correlates with poor patient prognosis, thereby serving as a potential biomarker for adverse outcomes in glioma. Functional enrichment and immune infiltration analyses reveal that ARHGDIB is implicated in the recruitment of immunosuppressive cells, such as M2 macrophages and neutrophils, contributing to the alteration of the glioma immunosuppressive microenvironment and hindering the immune response. Further investigations through single-cell sequencing, immunohistochemistry, immunofluorescence, and in vitro experiments demonstrate that ARHGDIB exhibits an expression pattern akin to CD163, with its overexpression inducing M2 macrophage polarization and facilitating glioma cell proliferation and migration.
ARHGDIB emerges as a novel marker for tumor-associated macrophages, playing a crucial role in shaping the immunosuppressive microenvironment and representing a promising prognostic biomarker for glioma.
胶质瘤是一种常见的颅内恶性肿瘤，由于其免疫抑制性微环境，治疗效果有限，导致患者预后不良。ARHGDIB参与肿瘤微环境的重塑，在各种肿瘤的发病机制中起重要作用。然而，其在胶质瘤免疫微环境中的调节作用仍不清楚。
利用公共数据库分析ARHGDIB的mRNA表达模式，并通过定量PCR（qPCR）和免疫组织化学（IHC）在我们收集的队列中进一步验证其表达。采用Kaplan-Meier生存分析和LASSO-Cox回归确定ARHGDIB在胶质瘤中的临床意义。随后，我们系统地评估了ARHGDIB表达与胶质瘤微环境内免疫特征之间的关联，以及其预测胶质瘤治疗反应的潜力。此外，进行了体外实验以阐明ARHGDIB在重塑胶质瘤微环境和促进肿瘤恶性进展中的作用。
结合公共数据库的生物信息学分析以及我们队列中的qPCR和IHC验证，我们的研究结果表明ARHGDIB在胶质瘤中明显过表达，并且与患者预后不良相关，从而作为胶质瘤不良结局的潜在生物标志物。功能富集和免疫浸润分析表明，ARHGDIB参与免疫抑制细胞的募集，如M2巨噬细胞和中性粒细胞，导致胶质瘤免疫抑制微环境的改变并阻碍免疫反应。通过单细胞测序、免疫组织化学、免疫荧光和体外实验的进一步研究表明，ARHGDIB表现出与CD163相似的表达模式，其过表达诱导M2巨噬细胞极化并促进胶质瘤细胞增殖和迁移。
ARHGDIB成为肿瘤相关巨噬细胞的一种新标志物，在塑造免疫抑制微环境中起关键作用，是胶质瘤一个有前景的预后生物标志物。
