CENPA acts as a prognostic factor that relates to immune infiltrates in gliomas

Bo Wang; Wei Wei; Shengrong Long; Lesheng Wang; Bin Yang; Du Wu; Zhengwei Li; Zhiqiang Li; Muhammad Arshad; Xiang Li; Jincao Chen

doi:10.3389/fneur.2022.1015221

CENPA acts as a prognostic factor that relates to immune infiltrates in gliomas

Front Neurol. 2022 Oct 19:13:1015221. doi: 10.3389/fneur.2022.1015221. eCollection 2022.

Authors

Bo Wang^{1

2}, Wei Wei^{1

2}, Shengrong Long^{1

2}, Lesheng Wang^{1

2}, Bin Yang^{1

2}, Du Wu^{1

2}, Zhengwei Li¹, Zhiqiang Li¹, Muhammad Arshad³, Xiang Li^{1

2}, Jincao Chen¹

Affiliations

¹ Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
² Brain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan, China.
³ Department of Biological Sciences, International Islamic University Islamabad, Islamabad, Pakistan.

Abstract

Background: Glioma is the most common primary tumor of the central nervous system (CNS). Centromere protein A (CENPA) plays an essential role in ensuring that mitosis proceeds normally. The effect of CENPA on glioma is rarely reported. However, the current study aims to explore whether aberrant CENPA expression promotes glioma progression and the potential mechanisms involved.

Methods: The GEPIA website, The Cancer Genome Atlas, and the Gene Expression Omnibus (GEO) were used to assess the expression of CENPA in glioma. The results were validated by real-time quantitative polymerase chain reaction and immunohistochemical staining of clinical samples. The relationship between the expression and prognostic value of the CENPA gene in glioma was investigated by Kaplan-Meier (KM) survival analysis with RNA-seq and clinical profiles downloaded from the Chinese Glioma Genome Atlas (CGGA) and UCSC Xena. The association between CENPA and clinical characteristics was also evaluated. Cell Counting Kit-8 (CCK8) assay, wound healing assay using two glioma cell lines, gene set enrichment analysis (GSEA), KEGG and gene ontology (GO) enrichment analysis, immune infiltration analysis, temozolomide (TMZ) sensitivity analysis, and single-cell sequence analysis were performed to explore the underlying mechanisms of high CENPA expression and its effect on glioma development. Finally, we performed a Cox analysis based on the expression of CENPA to predict patient prognosis.

Results: CENPA was significantly upregulated in glioma tissue samples and correlated with patient prognosis. Moreover, the downregulation of CENPA inhibited the migration and proliferation of glioma cells. In addition, the expression level of CENPA was significantly correlated with the grade, primary-recurrent-secondary (PRS) type, IDH mutation status, and 1p19q codeletion status. Furthermore, CENPA could serve as an independent prognostic factor for glioma that mainly interferes with the normal progression of mitosis and regulates the tumor immune microenvironment favoring glioma development.

Conclusion: CENPA may act as a prognostic factor in patients with glioma and provide a novel target for the treatment of gliomas.

Keywords: CENPA; CGGA; TCGA; glioma; tumor-infiltrating.