CD47 在胃癌中的表达与临床相关性及其与巨噬细胞浸润的关系。
CD47 expression in gastric cancer clinical correlates and association with macrophage infiltration.
机构信息
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
出版信息
Cancer Immunol Immunother. 2021 Jul;70(7):1831-1840. doi: 10.1007/s00262-020-02806-2. Epub 2021 Jan 3.
BACKGROUND
CD47 has been identified as an innate immune checkpoint and found to be associated with inferior survival in various types of cancer. However, the critical role of CD47 in gastric cancer and its association with tumor associated macrophages remain unclear.
METHODS
Tumor tissues of gastric cancer from Zhongshan Hospital and data from GSE62254, GSE84437 and TCGA datasets were analyzed. Immunohistochemistry was performed to detect the expression of CD47, CD11c, CD163 and CD68 in gastric cancer tissues. Kaplan-Meier curves and Cox model were used for comparing the clinical outcomes of patients belonging to different subgroups.
RESULTS
Gastric cancer patients with high CD47 expression exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT). A positive correlation was found between M1-polarized macrophage infiltration and CD47 expression in gastric cancer; however, the prognostic value of M1-polarized macrophages was attenuated in CD47-high gastric cancer patients. Moreover, we found that CD47 mRNA level was enriched in microsatellite-instable (MSI) subtype of gastric cancer and associated with ARID1A mutation and FGFR2 signaling pathway activation.
CONCLUSIONS
Aberrant CD47 expression represented an independent predictor for adverse survival outcome and ACT resistance in gastric cancer. Targeting CD47 might be a promising strategy for gastric cancer patients.
背景
CD47 已被确定为先天免疫检查点，并且在各种类型的癌症中与较差的生存相关。然而，CD47 在胃癌中的关键作用及其与肿瘤相关巨噬细胞的关系仍不清楚。
方法
分析了中山医院胃癌肿瘤组织和 GSE62254、GSE84437 和 TCGA 数据集的数据。进行免疫组织化学检测以检测胃癌组织中 CD47、CD11c、CD163 和 CD68 的表达。Kaplan-Meier 曲线和 Cox 模型用于比较不同亚组患者的临床结局。
结果
CD47 高表达的胃癌患者预后不良，对氟尿嘧啶为基础的辅助化疗（ACT）反应不佳。在胃癌中发现 M1 极化巨噬细胞浸润与 CD47 表达呈正相关；然而，在 CD47 高表达的胃癌患者中，M1 极化巨噬细胞的预后价值减弱。此外，我们发现 CD47 mRNA 水平在微卫星不稳定（MSI）型胃癌中富集，与 ARID1A 突变和 FGFR2 信号通路激活相关。
结论
异常表达 CD47 是胃癌患者不良生存结局和 ACT 耐药的独立预测因子。靶向 CD47 可能是胃癌患者的一种有前途的治疗策略。
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