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Bioinformatics analysis of the prognostic value of NEK8 and its effects on immune cell infiltration in glioma.

ABSTRACT: Glioma is the most common malignancy of the nervous system with high rates of recurrence and mortality, even after surgery. The 5-year survival rate is only about 5%. NEK8 is involved in multiple biological processes in a variety of cancers; however, its role in glioma is still not clear. In the current study, we evaluated the prognostic value of NEK8, as well as its role in the pathogenesis of glioma. Using a bioinformatics approach and RNA-seq data from public databases, we found that NEK8 expression is elevated in glioma tissues; we further verified this result by RT-PCR, Western blotting and immunochemistry using clinical samples. Functional enrichment analyses of genes with correlated expression indicated that elevated NEK8 expression is associated with increased immune cell infiltration in glioma and may affect the tumour microenvironment via the regulation of DNA damage/repair. Survival analyses revealed that high levels of NEK8 are associated with a poorer prognosis; higher WHO grade, IDH status, 1p/19q codeletion, age and NEK8 were identified as an independent prognostic factor. These findings support the crucial role of NEK8 in the progression of glioma via effects on immune cell infiltration and suggest that it is a new prognostic biomarker.

SUBMITTER: Xiao M

PROVIDER: S-EPMC8435421 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Bioinformatics analysis of the prognostic value of NEK8 and its effects on immune cell infiltration in glioma.

Xiao Meng M Du Chaoyang C Zhang Chuanbo C Zhang Xinzhong X Li Shaomin S Zhang Dainan D Jia Wang W

Journal of cellular and molecular medicine 20210810 18

Glioma is the most common malignancy of the nervous system with high rates of recurrence and mortality, even after surgery. The 5-year survival rate is only about 5%. NEK8 is involved in multiple biological processes in a variety of cancers; however, its role in glioma is still not clear. In the current study, we evaluated the prognostic value of NEK8, as well as its role in the pathogenesis of glioma. Using a bioinformatics approach and RNA-seq data from public databases, we found that NEK8 exp ...[more]

PMID: 34374193

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Project description:Background Cutaneous melanoma (CM) has a poor overall prognosis. Immune checkpoint inhibitor (ICI) therapy effectively improves overall survival in individuals with advanced melanoma, but only some patients benefit. Serpin Family A Member 1 (SERPINA1), a type of proteinase inhibitor that is used for many targets, is abnormally expressed and plays a vital role in multiple cancers. However, little is known about the clinical significance of SERPINA1 in CM. Methods The Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) datasets were used to compare SERPINA1 expression levels. The association between SERPINA1 and other clinical factors were examined with R software, and receiver operating characteristic (ROC) curves for identification was developed. The Tumor IMmune Estimation Resource (TIMER) was used to examine the invasion of immune cells, markers for immune cells, and immunological checkpoints. The predictive value of SERPINA1 DNA methylation levels for every CpG was analyzed with the MethSurv web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to assess the roles of genes that interacted with SERPINA1. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict SERPINA1’s response to ICIs. Results SERPINA1 was substantially expressed in CM. Overexpression of SERPINA1 was significantly associated with CM severity. The outcome for individuals with elevated SERPINA1 expression was good (HR =0.54, P<0.001). Using SERPINA1 expression levels, tumors and normal tissues could be reliably differentiated [area under the curve (AUC) =0.889]. Positive associations were found between SERPINA1 in CM and the infiltration of immune cells and immunological checkpoints [programmed cell death-1 (PD-1) and CTLA-4]. The efficacy of immune checkpoint blockade (ICB) in patients with a low expression of SERPINA1 was good. The GO pathway enrichment analysis showed that activation of neutrophil granulocytes participated in enrichment in the immune response pathway. Patients with low SERPINA1 expression had low TIDE scores. Conclusions SERPINA1 is involved not only in the development and progression of CM but also in the immunological control of CM. Thus, SERPINA1 may serve as a possible biomarker for CM diagnosis, as well as its therapeutic target.

Project description:Gliomas are difficult-to-treat brain tumors due to their aggressive nature, rapid proliferation, and high invasiveness (Zhang et al., J Cell Biochem, 2019, 120 (9), 15106-15118; Ge et al., Int J Biochem Cell Biol, 2021, 139, 106054). FOXD3-AS1 has been identified as an emerging potential target for tumor prediction and treatment in many studies (Qin et al., Front Oncol, 2021, 11, 688027). However, the utility of FOXD3-AS1 has not been reported in glioma patients (Li et al., Cancer Manag Res, 2021, 13, 9037-9048). The differential profiles of FOXD3-AS1 in TCGA-GBMLGG database were analyzed across clinical subgroups. The analysis of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) revealed that a high level of FOXD3-AS1 was associated with a poor prognosis and survival outcome. Based on the Cox regression analysis, FOXD3-AS1 was found to be a high-risk factor for glioma that affects prognosis outcomes independently. More importantly, because oxidative stress is closely linked to glioma prognosis, we focused on the potential mechanisms of six oxidative stress co-expressed genes with FOXD3-AS1. In addition, the predictive value of FOXD3-AS1 was determined for each clinical subgroup status. The ROC curve results showed that FOXD3-AS1 had a good predictive performance. A stratified clinicopathological subgroup analysis revealed that high expression of FOXD3-AS1 is associated with a poor prognosis. This also indicates a link between FOXD3-AS1 and tumorigenesis and prognosis, which has potential application value. Furthermore, the immune cell infiltration of FOXD3-AS1 and the signal marker correlation suggested that immune cell infiltration differed significantly between immune cell subsets. To the best of our knowledge, this is the first report to investigate FOXD3-AS1 in glioma and how it may modulate GBM and LGG immune microenvironments. Furthermore, FOXD3-AS1 was detected in tumor and paraneoplastic tissues using RT-qPCR. Transwell analysis verified the migration and invasion of the FOXD3-AS1 knockout group in vitro to a certain extent. In conclusion, FOXD3-AS1 can be used as a prognostic indicator for GBM and LGG, and it is closely related to immune infiltration and response to oxidative stress, which may contribute to the advancement of glioma immunotherapy research.

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Project description:BackgroundIn recent decades, there has been increasing evidence that Go-Ichi-Nii-San (GINS) subunits play an important role in the development and progression of various tumors. However, little research has been conducted on the role of GINS subunits in clear cell renal cell carcinoma (ccRCC). This study sought to explore the differential expression, prognosis, and immunological significance of GINS subunits in ccRCC.MethodsWe used various analysis packages of R (version 3.6.3), the University of ALabama at Birmingham CANcer (UALCAN) data analysis portal, the Cancer Cell Line Encyclopedia (CCLE), the cBio Cancer Genomics Portal (cBioPortal), and the Tumor Immune Estimation Resource (TIMER) to study the gene expression, promoter methylation level, gene mutations, prognostic and diagnostic value, immune infiltration, pathway enrichment, and other aspects of the GINS subunits. Next, the genes related to the GINS subunits were analyzed using the STRING and GeneMANIA platforms, and the correlation between GINS subunits and the functions involved were investigated.ResultsThe expression level of GINS1/2/3/4 was significantly higher in ccRCC tumor tissues than normal tissues, and was significantly related to tumor grade and stage. The expression of GINS1/2/4 may be related to the methylation degree of the promoter region. The prognostic and diagnostic analyses showed that the increased expression of GINS1 was associated with various poor prognoses and had diagnostic value. The GINS subunit mutation also significantly affected the clinical prognosis of ccRCC patients. Finally, the correlation analysis of the immune infiltration level, co-expression, and enrichment of related genes indicated that GINS subunit expression was associated with different levels of ccRCC immune infiltration.ConclusionsThe analysis results showed that the differential expression of GINS subunits in ccRCC, which had prognostic and diagnostic value, was correlated with clinicopathological stage, immune infiltration, and other related aspects. GINS1 may serve as a new potential prognostic biomarker for ccRCC patients and be used to guide treatment.

Dataset Information

Bioinformatics analysis of the prognostic value of NEK8 and its effects on immune cell infiltration in glioma.

Publications

Bioinformatics analysis of the prognostic value of NEK8 and its effects on immune cell infiltration in glioma.

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