CD24影响多种癌症中肿瘤浸润细胞的免疫抑制作用和肿瘤抗性。

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

作者信息

Zhao Chunmei, Huang Ying, Zhang Haotian, Liu Huimin

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China.

Department of Clinical Laboratory, Qidong People's Hospital/Affiliated Qidong Hospital of Nantong University, Nantong, Jiangsu, China.

出版信息

Discov Oncol. 2024 Sep 2;15(1):399. doi: 10.1007/s12672-024-01284-7.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker.

背景

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。

方法

使用TIMER分析22种免疫细胞与CD24表达之间的相关性。使用R包“ESTIMATE”预测泛癌中免疫细胞和基质细胞的比例。进行Spearman相关性分析以评估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和蛋白质印迹以评估肝细胞癌（LIHC）中CD24的表达水平。此外，对LIHC中的CD24进行功能缺失以进行生物学评估。

结果

在各种肿瘤中，如膀胱癌（BLCA）、人乳头瘤病毒阳性的头颈部鳞状细胞癌（HNSC-HPV）、头颈部鳞状细胞癌（HNSC）、肾嫌色细胞癌（KICH）、肾透明细胞癌（KIRC）、肾乳头状细胞癌（KIRP）、睾丸生殖细胞肿瘤（TGCT）、甲状腺癌（THCA）、胸腺瘤（THYM）和子宫内膜癌（UCEC），CD24表达与髓样细胞（包括中性粒细胞和髓源性抑制细胞）呈正相关。相反，在乳腺癌-人表皮生长因子受体2（BRCA-Her2）、食管癌（ESCA）、人乳头瘤病毒阳性的头颈部鳞状细胞癌（HNSC-HPV）、肾透明细胞癌（KIRC）、甲状腺癌（THCA）和胸腺瘤（THYM）中，抗肿瘤自然杀伤细胞（NK细胞）和自然杀伤T细胞（NKT细胞）与CD24表达呈负相关。CD24与免疫评分相关性最高的前三种肿瘤是睾丸生殖细胞肿瘤（TGCT）、甲状腺癌（THCA）和皮肤黑色素瘤（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。在子宫颈癌（CESC）、胆管癌（CHOL）、结肠癌（COAD）、食管癌（ESCA）、直肠癌（READ）、睾丸生殖细胞肿瘤（TGCT）和甲状腺癌（THCA）中，免疫检查点和趋化因子也与CD24呈负相关。此外，CD24在大多数肿瘤中过表达，在乳腺癌（BRCA）、肝细胞癌（LIHC）和子宫颈癌（CESC）中高表达与预后不良相关。TIDE数据库表明，CD24高表达的肿瘤，尤其是黑色素瘤，对PD1/PD-L1免疫治疗反应较差。最后，CD24敲低导致LIHC中增殖和细胞周期进程受损。