Integrated profiling identifies ferredoxin 1 as an immune-related biomarker of malignant phenotype in glioma

Dongcheng Xie; Hailong Huang; Youwei Guo; Zhipeng Jiang; Yirui Kuang; Haoxuan Huang; Weidong Liu; Lei Wang; Zhaoqi Xin; Binbin Wang; Caiping Ren; Xingjun Jiang

Heliyon (Mar 2024)

Integrated profiling identifies ferredoxin 1 as an immune-related biomarker of malignant phenotype in glioma

Dongcheng Xie,
Hailong Huang,
Youwei Guo,
Zhipeng Jiang,
Yirui Kuang,
Haoxuan Huang,
Weidong Liu,
Lei Wang,
Zhaoqi Xin,
Binbin Wang,
Caiping Ren,
Xingjun Jiang

Affiliations

Dongcheng Xie: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Hailong Huang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Youwei Guo: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Zhipeng Jiang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Yirui Kuang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Haoxuan Huang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Weidong Liu: Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China; The NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
Lei Wang: Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China; The NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China
Zhaoqi Xin: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Corresponding author.
Binbin Wang: Department of Neurosurgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, China; Corresponding authors.
Caiping Ren: Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China; The NHC Key Laboratory of Carcinogenesis and The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, China; Corresponding author. Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
Xingjun Jiang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Corresponding authors.

Journal volume & issue: Vol. 10, no. 5
p. e26976

Abstract

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Background: Glioma, a highly resistant and recurrent type of central nervous system tumor, poses a significant challenge in terms of effective drug treatments and its associated mortality rates. Despite the discovery of Ferredoxin 1 (FDX1) as a crucial participant in cuproptosis, an innovative mechanism of cellular demise, its precise implications for glioma prognosis and tumor immune infiltration remain inadequately elucidated. Methods: To analyze pan-cancer data, we employed multiple public databases. Gene expression evaluation was performed using tissue microarray (TMA) and single-cell sequencing data. Furthermore, four different approaches were employed to assess the prognostic importance of FDX1 in glioma. We conducted the analysis of differential expression genes (DEGs) and Gene Set Enrichment Analysis (GSEA) to identify immune-related predictive signaling pathways. Somatic mutations were assessed using Tumor Mutation Burden (TMB) and waterfall plots. Immune cell infiltration was evaluated with five different algorithms. Furthermore, we performed in vitro investigations to evaluate the biological roles of FDX1 in glioma. Results: Glioma samples exhibited upregulation of FDX1, which in turn predicted poor prognosis and was positively associated with unfavorable clinicopathological characteristics. Notably, the top four enriched signaling pathways were immune-related, and the discovery revealed a connection between the expression of FDX1 and the frequency of mutations or the TMB. The FDX1_high group exhibited heightened infiltration of immune cells, and there existed a direct association between the expression of FDX1 and the regulation of immune checkpoint. In vitro experiments demonstrated that FDX1 knockdown reduced proliferation, migration, invasion and transition from G2 to M phase in glioma cells. Conclusion: In glioma, FDX1 demonstrated a positive association with the advancement of malignancy and changes in the infiltration of immune cells.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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