IGFBP2 from a novel copper metabolism-associated biomarker promoted glioma progression and response to immunotherapy

Qisheng Luo; Junhong Zhuang; Dandan Zheng; Changfeng Miao; Hongcheng Luo; Jun Peng; Chuanhua Zheng; Chengjian Qin; Chuanliu Lan; Meiqin Chen; Ying Xia; Deyou Huang; Zigui Chen

doi:10.3389/fimmu.2023.1282734

IGFBP2 from a novel copper metabolism-associated biomarker promoted glioma progression and response to immunotherapy

Front Immunol. 2023 Oct 19:14:1282734. doi: 10.3389/fimmu.2023.1282734. eCollection 2023.

Authors

Qisheng Luo¹, Junhong Zhuang², Dandan Zheng³, Changfeng Miao⁴, Hongcheng Luo⁵, Jun Peng⁶, Chuanhua Zheng¹, Chengjian Qin¹, Chuanliu Lan¹, Meiqin Chen⁷, Ying Xia⁶, Deyou Huang⁸, Zigui Chen⁶

Affiliations

¹ Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
² Department of Neurology, Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou, China.
³ Department of Radiation Oncology, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
⁴ Department of Laboratory Medicine, Neurosurgery Second Branche, Hunan Provincial People's Hospital (The First affiliated Hospital of Hunan Normal University), Changsha, Hunan, China.
⁵ Department of Laboratory Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
⁶ Department of Neurosurgery, Affiliated Haikou Hospital of Xiangya Medical School, Central South University, Haikou, China.
⁷ Department of Radiation Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.
⁸ Department of Radiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.

Abstract

Introduction: Copper metabolism encompasses all cellular metabolic processes involving copper ions and plays a significant role in the pathogenesis of diseases, including cancer. Furthermore, copper is intricately involved in various processes related to nucleotide metabolism. However, a comprehensive analysis of copper metabolism in gliomas remains lacking despite its importance.

Methods: To address this gap, glioma patients were stratified based on the expression levels of copper metabolism-related genes. By utilizing machine learning techniques, a novel copper metabolism-associated biomarker was developed. The potential of this biomarker in prognosis, mutation analysis, and predicting immunotherapy response efficiency in gliomas was systematically investigated.

Results: Notably, IGFBP2, identified as a glioma tumor promoter, was found to promote disease progression and influence immunotherapy response. Additionally, glioma-derived IGFBP2 was observed to enhance microglial migration. High IGFBP2 expression in GBM cells facilitated macrophage interactions through the EGFR, CD63, ITGB1, and CD44 signaling pathways. Discussion: Overall, the copper metabolism-associated biomarker shows promising potential to enhance the clinical management of gliomas, offering valuable insights into disease prognosis and treatment strategies.

Keywords: IGFBP2; copper metabolism; gliomas; immunotherapy; nucleotide metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Brain Neoplasms* / genetics
Copper
Glioma* / genetics
Humans
Immunotherapy

Substances

Copper
Biomarkers

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. Haikou People’s Hospital to introduce high-level talent project in 2022 (grant no. 20220812); Project supported by Hainan Province Clinical Medical Center (LCYX202107, LCYX202309); Natural Science Foundation of Guangxi Zhuang Autonomous Region (2020GXNSFAA297108); Jinhua Science and Technology Research Plan Project (2021-4-013).