铜蓝蛋白与免疫细胞浸润相关,并在胶质瘤患者中作为预后生物标志物发挥作用。
Ceruloplasmin is associated with the infiltration of immune cells and acts as a prognostic biomarker in patients suffering from glioma.
发表日期:2023
作者:
Miaomiao Jia, Tianyu Dong, Yangyang Cheng, Fanghao Rong, Jiamin Zhang, Wei Lv, Shuman Zhen, Xianxian Jia, Bin Cong, Yuming Wu, Huixian Cui, Peipei Hao
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
胶质瘤被视为侵袭性生长模式和低临床治愈率的中枢神经系统(CNS)常见癌症形式。尽管在过去十年中外科切除、化学放射治疗和免疫治疗的治疗策略有所进展,但临床结果仍然不容乐观,这归因于胶质瘤的低免疫原性和肿瘤微环境(TME)。多功能分子称为铜蓝蛋白(CP)参与铁代谢。对CP在胶质瘤患者中的表达模式、预后意义以及与免疫细胞的关联尚未深入研究。使用中国胶质瘤基因组图谱(CGGA)、癌症基因组图谱(TCGA)和Gliovis等多个数据库的研究表明,患有胶质瘤的患者中CP的mRNA和蛋白表达水平随胶质瘤分级的增加而显著增加。Kaplan-Meier(KM)曲线和统计检验突显了CP表达水平升高患者存活时间显著缩短。根据Cox回归分析,CP可以作为胶质瘤患者的独立预测性生物标记物。Gene Ontology(GO)、Kyoto Encyclopedia of Genes and Genomes(KEGG)和Gene Set Enrichment Analysis(GSEA)对数据进行分析后发现CP表达与多个免疫相关通路显著相关。肿瘤免疫评估资源(TIMER)和CIBERSORT分析显示CP表达与TME中免疫细胞浸润之间存在显著相关性。此外,胶质瘤中免疫检查点和CP表达呈良好关联。根据这些结果,患有胶质瘤的患者在CP表达低时具有更好的预后和肿瘤免疫细胞浸润水平。因此,CP可能可以作为胶质瘤的潜在治疗靶点,并可能预测免疫治疗的有效性。Copyright © 2023 Jia, Dong, Cheng, Rong, Zhang, Lv, Zhen, Jia, Cong, Wu, Cui and Hao.
Glioma is regarded as a prevalent form of cancer that affects the Central Nervous System (CNS), with an aggressive growth pattern and a low clinical cure rate. Despite the advancement of the treatment strategy of surgical resection, chemoradiotherapy and immunotherapy in the last decade, the clinical outcome is still grim, which is ascribed to the low immunogenicity and tumor microenvironment (TME) of glioma. The multifunctional molecule, called ceruloplasmin (CP) is involved in iron metabolism. Its expression pattern, prognostic significance, and association with the immune cells in gliomas have not been thoroughly investigated. Studies using a variety of databases, including Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gliovis, showed that the mRNA and protein expression levels of CP in patients suffering from glioma increased significantly with an increasing glioma grade. Kaplan-Meier (KM) curves and statistical tests highlighted a significant reduction in survival time of patients with elevated CP expression levels. According to Cox regression analysis, CP can be utilized as a stand-alone predictive biomarker in patients suffering from glioma. A significant association between CP expression and numerous immune-related pathways was found after analyzing the data using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Tumor Immune Estimation Resource (TIMER) and CIBERSORT analyses indicated a substantial correlation between the CP expression and infiltration of immunocytes in the TME. Additionally, immune checkpoints and CP expression in gliomas showed a favorable correlation. According to these results, patients with glioma have better prognoses and levels of tumor immune cell infiltration when their CP expression is low. As a result, CP could be used as a probable therapeutic target for gliomas and potentially anticipate the effectiveness of immunotherapy.Copyright © 2023 Jia, Dong, Cheng, Rong, Zhang, Lv, Zhen, Jia, Cong, Wu, Cui and Hao.