Ceruloplasmin is associated with the infiltration of immune cells and acts as a prognostic biomarker in patients suffering from glioma

Abstract

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.

Transcriptomic Hallmarks of Mortality Reveal Universal and Specific Mechanisms of Aging, Chronic Disease, and Rejuvenation

“…Genes driving aging-and mortality-associated effect of Klotho KO in proximal tubule cells were similar to those in the bulk kidney (Pearson's r = 0.57) (Extended Data Fig. 15A-C), including upregulated Cdkn1a and Cp, the latter encoding ceruloplasmin glycoprotein involved in iron metabolism and shown to be elevated in multiple disease models, including HCC, glioma, heart failure, and cerebral ischemia [95][96][97][98] . At the same time, although neurons also exhibited an acceleration of tAge in Klotho KO model, it was associated with distinct molecular signatures of mortality, not significantly correlated with those in proximal tubules (Pearson's r = 0.02) and weakly correlated with those in skeletal muscle (Pearson's r = 0.11) (Extended Data Fig.…”