研究动态
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CD24影响多种癌症中肿瘤浸润细胞的免疫抑制作用和肿瘤抵抗力。

CD24 affects the immunosuppressive effect of tumor-infiltrating cells and tumor resistance in a variety of cancers.

发表日期:2024 Sep 02
作者: Chunmei Zhao, Ying Huang, Haotian Zhang, Huimin Liu
来源: Immunity & Ageing

摘要:

分化簇 24 (CD24) 是一种高度糖基化的糖基磷脂酰肌醇 (GPI) 锚定表面蛋白,在多种肿瘤细胞中表达,作为肿瘤免疫中的“别吃我”信号分子。本研究旨在探讨CD24在泛癌中的潜在特征。采用TIMER分析22种免疫细胞与CD24表达的相关性。 R包“ESTIMATE”用于预测泛癌中免疫细胞和基质细胞的比例。采用 Spearman 相关分析评估 CD24 表达与免疫检查点、趋化因子、错配修复、肿瘤突变负荷和微卫星不稳定性之间的关系,并进行 qPCR 和蛋白质印迹评估肝细胞癌 (LIHC) 中 CD24 表达水平。此外,对LIHC中CD24的功能丧失进行了生物学评估。在多种肿瘤中,例如BLCA、HNSC-HPV、HNSC、KICH,CD24表达与骨髓细胞(包括中性粒细胞和骨髓源性抑制细胞)呈正相关。 、KIRC、KIRP、TGCT、THCA、THYM 和 UCEC。相反,抗肿瘤 NK 细胞和 NKT 细胞与 BRCA-Her2、ESCA、HNSC-HPV、KIRC、THCA 和 THYM 中的 CD24 表达呈负相关。 CD24与ImmuneScore相关性最高的前三名肿瘤是TGCT、THCA和SKCM。功能富集分析显示 CD24 表达与各种免疫相关途径呈负相关。免疫检查点和趋化因子在 CESC、CHOL、COAD、ESCA、READ、TGCT 和 THCA 中也表现出与 CD24 呈负相关。此外,CD24 在大多数肿瘤中过度表达,其中 BRCA、LIHC 和 CESC 中 CD24 高表达与不良预后相关。 TIDE 数据库表明,CD24 高表达的肿瘤,尤其是黑色素瘤,对 PD1/PD-L1 免疫疗法的反应较差。最后,CD24 敲低导致 LIHC 中的增殖和细胞周期进展受损。CD24 参与免疫浸润的调节,影响患者预后并作为潜在的肿瘤标志物。© 2024。作者。
Cluster of differentiation 24 (CD24) is a highly glycosylated glycosylphosphatidylinositol (GPI)-anchored surface protein, expressed in various tumor cells, as a "don't eat me" signaling molecule in tumor immune. This study aimed to investigate the potential features of CD24 in pan-cancer.The correlations between 22 immune cells and CD24 expression were using TIMER analysis. R package "ESTIMATE" was used to predict the proportion of immune and stromal cells in pan-cancer. Spearman's correlation analysis was performed to evaluate the relationships between CD24 expression and immune checkpoints, chemokines, mismatch repair, tumor mutation burden and microsatellite instability, and qPCR and western blot were conducted to assess CD24 expression levels in liver hepatocellular carcinoma (LIHC). In addition, loss of function was performed for the biological evaluation of CD24 in LIHC.CD24 expression was positively correlated with myeloid cells, including neutrophils and myeloid-derived suppressor cells, in various tumors, such as BLCA, HNSC-HPV, HNSC, KICH, KIRC, KIRP, TGCT, THCA, THYM, and UCEC. In contrast, anti-tumor NK cells and NKT cells showed a negative association with CD24 expression in BRCA-Her2, ESCA, HNSC-HPV, KIRC, THCA, and THYM. The top three tumors with the highest correlation between CD24 and ImmuneScore were TGCT, THCA, and SKCM. Functional enrichment analysis revealed CD24 expression was negatively associated with various immune-related pathways. Immune checkpoints and chemokines also exhibited inverse correlations with CD24 in CESC, CHOL, COAD, ESCA, READ, TGCT, and THCA. Additionally, CD24 was overexpressed in most tumors, with high CD24 expression in BRCA, LIHC, and CESC correlating with poor prognosis. The TIDE database indicated tumors with high CD24 expression, particularly melanoma, were less responsive to PD1/PD-L1 immunotherapy. Finally, CD24 knockdown resulted in impaired proliferation and cell cycle progression in LIHC.CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker.© 2024. The Author(s).