PO.TB10.08 · 肿瘤生物学
Gli1高表达肿瘤细胞与M2巨噬细胞之间的空间相互作用可预测胃癌的生存和复发
Spatial interaction between Gli1 high tumor cells and M2 macrophages predicts survival and recurrence in gastric cancer
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摘要 Abstract
中文摘要
目的:本研究通过分析GLI1表达与CD163和CD206所标识的肿瘤相关M2巨噬细胞的浸润和空间邻近性之间的关联,探讨GLI1表达在胃癌中的预后意义。我们评估了GLI1-M2巨噬细胞联合空间表型如何影响临床结局,包括生存和复发模式。
方法:使用免疫组化和空间生物学方法(包括多重免疫荧光和基于机器学习的数字病理学)评估GLI1表达和M2巨噬细胞浸润。CD163和CD206用于定义M2巨噬细胞群。空间指标包括GLI1表达强度、M2巨噬细胞密度以及GLI1阳性肿瘤细胞与CD163/CD206阳性巨噬细胞之间的细胞间距离。使用Kaplan-Meier生存曲线和多变量Cox回归分析其与临床结局的关联。
结果:高GLI1表达与CD163/CD206阳性M2巨噬细胞浸润增加(p=0.001)以及肿瘤细胞与M2巨噬细胞之间空间距离缩短(p=0.01)呈强相关。GLI1高且M2邻近的表型与总生存显著缩短、复发率(包括早期复发)升高以及富含免疫抑制和促肿瘤信号的微环境相关。相比之下,GLI1表达较低且与M2巨噬细胞分离更远的肿瘤显示出更好的生存结局和更低的复发。
结论:GLI1表达和CD163/CD206阳性M2巨噬细胞的空间邻近性可作为胃癌的强预后指标。GLI1高且M2邻近的表型识别出一个临床上脆弱、结局显著更差的亚组。这些发现凸显了GLI1-M2巨噬细胞轴的生物学相关性,并提示靶向GLI1信号或重编程M2巨噬细胞可能带来治疗获益并降低胃癌的复发风险。
查看英文原文 English abstract
Purpose: This study investigated the prognostic significance of GLI1 expression in gastric cancer by analyzing its association with the infiltration and spatial proximity of tumor-associated M2 macrophages identified by CD163 and CD206. We evaluated how the combined GLI1-M2 macrophage spatial phenotype influences clinical outcomes, including survival and recurrence patterns.
Methods: GLI1 expression and M2 macrophage infiltration were assessed using immunohistochemistry and spatial biology approaches, including multiplex immunofluorescence and machine-learning-based digital pathology. CD163 and CD206 defined M2 macrophage populations. Spatial metrics included GLI1 expression intensity, M2 macrophage density, and the intercellular distance between GLI1-positive tumor cells and CD163/CD206-positive macrophages. Associations with clinical outcomes were analyzed using Kaplan-Meier survival curves and multivariate Cox regression.
Results: High GLI1 expression demonstrated a strong correlation with increased infiltration of CD163/CD206-positive M2 macrophages (p=0.001) and reduced spatial distance between tumor cells and M2 macrophages (p=0.01). The GLI1-high and M2-close phenotype was associated with markedly reduced overall survival, higher recurrence rates including early relapse, and a microenvironment enriched with immunosuppressive and tumor-promoting signals. In contrast, tumors with lower GLI1 expression and greater separation from M2 macrophages showed improved survival outcomes and reduced recurrence.
Conclusions: GLI1 expression and the spatial proximity of CD163/CD206-positive M2 macrophages serve as strong prognostic indicators in gastric cancer. The GLI1-high and M2-close phenotype identifies a clinically vulnerable subgroup with significantly poorer outcomes. These findings highlight the biological relevance of the GLI1-M2 macrophage axis and suggest that targeting GLI1 signaling or reprogramming M2 macrophages may provide therapeutic benefit and reduce recurrence risk in gastric cancer.
利益披露 Disclosure
D. Kim, None.