Jia Miaomiao, Dong Tianyu, Cheng Yangyang, Rong Fanghao, Zhang Jiamin, Lv Wei, Zhen Shuman, Jia Xianxian, Cong Bin, Wu Yuming, Cui Huixian, Hao Peipei
Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei, China.
International Cooperation Laboratory of Stem Cell Research, Shijiazhuang, China.
Front Pharmacol. 2023 Aug 11;14:1249650. doi: 10.3389/fphar.2023.1249650. eCollection 2023.
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.
胶质瘤被认为是一种影响中枢神经系统(CNS)的常见癌症形式,具有侵袭性生长模式和较低的临床治愈率。尽管在过去十年中手术切除、放化疗和免疫治疗等治疗策略取得了进展,但临床结果仍然严峻,这归因于胶质瘤的低免疫原性和肿瘤微环境(TME)。称为铜蓝蛋白(CP)的多功能分子参与铁代谢。其在胶质瘤中的表达模式、预后意义以及与免疫细胞的关联尚未得到充分研究。使用包括中国胶质瘤基因组图谱(CGGA)、癌症基因组图谱(TCGA)和Gliovis在内的各种数据库进行的研究表明,胶质瘤患者中CP的mRNA和蛋白质表达水平随着胶质瘤分级的增加而显著升高。Kaplan-Meier(KM)曲线和统计测试突出显示CP表达水平升高的患者生存时间显著缩短。根据Cox回归分析,CP可作为胶质瘤患者的独立预测生物标志物。在使用基因本体论(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)分析数据后,发现CP表达与众多免疫相关途径之间存在显著关联。肿瘤免疫估计资源(TIMER)和CIBERSORT分析表明CP表达与TME中免疫细胞的浸润之间存在显著相关性。此外,胶质瘤中的免疫检查点与CP表达呈良好相关性。根据这些结果,CP表达低的胶质瘤患者预后较好,肿瘤免疫细胞浸润水平较高。因此,CP可作为胶质瘤的潜在治疗靶点,并有可能预测免疫治疗的效果。