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

Miaomiao Jia; Tianyu Dong; Yangyang Cheng; Fanghao Rong; Jiamin Zhang; Wei Lv; Shuman Zhen; Xianxian Jia; Bin Cong; Yuming Wu; Huixian Cui; Peipei Hao

doi:10.3389/fphar.2023.1249650

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

Front Pharmacol. 2023 Aug 11:14:1249650. doi: 10.3389/fphar.2023.1249650. eCollection 2023.

Authors

Miaomiao Jia^{1

2

3

4}, Tianyu Dong^{1

2}, Yangyang Cheng⁵, Fanghao Rong^{1

2}, Jiamin Zhang^{1

2}, Wei Lv⁶, Shuman Zhen⁶, Xianxian Jia⁴, Bin Cong⁴, Yuming Wu⁷, Huixian Cui^{1

2

8}, Peipei Hao^{1

2

8}

Affiliations

¹ Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei, China.
² International Cooperation Laboratory of Stem Cell Research, Shijiazhuang, China.
³ Postdoctoral Mobile Station of Biology, Hebei Medical University, Shijiazhuang, Hebei, China.
⁴ Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Hebei Medical University, Shijiazhuang, Hebei, China.
⁵ Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁶ Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
⁷ Hebei Collaborative Innovation Center for Cardio Cerebrovascular Disease, Department of Physiology, Hebei Medical University, Shijiazhuang, China.
⁸ Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Shijiazhuang, China.

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.

Keywords: Chinese Glioma Genome Atlas (CGGA); The Cancer Genome Atlas (TCGA); ceruloplasmin (CP); gliomas; tumor immune microenvironment (TIME).

Grants and funding

This work was supported by the Postdoctoral Fund of Hebei Medical University, Postdoctoral Fund of Hebei Province (B2022003035), the Medical Science Research Project of Health Commission of Hebei Province (20231547), the CAMS Innovation Fund for Medical Sciences (2019-12M-5-055), and the Hebei Medical University Chunyu Project (CYQD2023007 and CYYQ201901), and the Natural Science Foundation of Hebei Province (H2020206524).