High Expression of CISD2 in Relation to Adverse Outcome and Abnormal Immune Cell Infiltration in Glioma

Author:

Zhang Fang12ORCID,Cai Hua-Bao2ORCID,Liu Han-Ze2ORCID,Gao Shen3ORCID,Wang Bin2ORCID,Hu Yang-Chun2ORCID,Cheng Hong-Wei2ORCID,Liu Jin-Xiu1ORCID,Gao Yang1ORCID,Hong Wen-Ming24ORCID

Affiliation:

1. School of Nursing, Anhui Medical University, Hefei 230032, China

2. Department of Neurosurgery, First Affiliated Hospital of Anhui Medical University, Hefei 230032, China

3. School of Clinical Medicine, Wan-Nan Medical College, Wuhu 241000, China

4. Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China

Abstract

Glioma is a serious disease burden globally, with high mortality and recurrence rates. CDGSH iron sulfur domain 2 (CISD2) is an evolutionarily conserved protein that is involved in several cancers. However, its role in the prognosis and immune infiltration in glioma remains unclear. In our research, RNA-seq matrix and clinicopathological relevant data for CISD2 were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Human Protein Atlas was used to verify the CISD2 protein level in glioma, and STRING was used to establish relative coexpression gene network. The Kaplan-Meier plotter was adopted to analyze the effect of CISD2 on prognosis. The connection between CISD2 expression and immune infiltration was analyzed using single-sample GSEA (ssGSEA), TIMER, and GEPIA. In contrast to normal tissues, CISD2 expression was significantly higher in glioma tissues, and CISD2 presented a certain diagnostic value in distinguishing glioma tissues from normal tissues. Furthermore, the CISD2 level was correlated with age, histologic grade, histological type, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion status, and primary therapy outcome of glioma, while high CISD2 mRNA expression was correlated with grave overall survival. Multivariate analysis demonstrated that CISD2 was an independent risk factor for patients with glioma. Functional enrichment analysis indicated that CISD2 could regulate proliferation, immune reaction, and mitochondrial function. The results from the ssGSEA and TIMER databases confirmed that CISD2 acts a prominent role in immune cell infiltration in the tumor microenvironment, especially in low-grade glioma (LGG). Furthermore, CISD2 expression was observably correlated to M2 polarization in macrophages with glioma progression. This is the first research to investigate the immune role of CISD2 in glioma. CISD2 may be an innovative prognostic biomarker and can act as a potential target for future therapy for glioma.

Funder

Open Project of Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education

Publisher

Hindawi Limited

Subject

Biochemistry (medical),Clinical Biochemistry,Genetics,Molecular Biology,General Medicine

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