Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma
BackgroundAs a novel form of programmed cell death, necroptosis is related to multiple tumor types and their immune microenvironments. However, its association with glioma has not been clarified.MethodsNecroptosis genes were obtained from the Gene Set Enrichment Analysis (GSEA) database. RNA-seq and...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.855434/full |
| _version_ | 1817978714005176320 |
|---|---|
| author | Zunjie Zhou Jing Xu Ning Huang Jun Tang Ping Ma Yuan Cheng |
| author_facet | Zunjie Zhou Jing Xu Ning Huang Jun Tang Ping Ma Yuan Cheng |
| author_sort | Zunjie Zhou |
| collection | DOAJ |
| description | BackgroundAs a novel form of programmed cell death, necroptosis is related to multiple tumor types and their immune microenvironments. However, its association with glioma has not been clarified.MethodsNecroptosis genes were obtained from the Gene Set Enrichment Analysis (GSEA) database. RNA-seq and clinical data were downloaded from TCGA and CGGA databases. A necroptosis gene signature was constructed based on univariate and multivariate Cox regression analyses. Next, survival analysis, independent prognostic analysis, and nomogram were performed to assess and verify the model. Subsequently, we analyzed the tumor microenvironment (TME) and immune cell infiltration via ESTIMATE and CIBERSORTx algorithms. Finally, the response of glioma patients in the TCGA database to immune checkpoint inhibitor (ICI) therapy was predicted using the Tumor Immune Dysfunction and Exclusion (TIDE) database.ResultsOf the seven prognostic necroptosis genes, RIPK1, RIPK3, FAS, and FADD were used to construct the risk signature that accurately predicts the prognosis of glioma patients. Functional enrichment results suggest that necroptosis is correlated with immune response and angiogenesis. Immune analysis revealed that necroptosis can boost inflammatory activity and attract immunosuppressive cell infiltration to form a chronic inflammatory microenvironment, promoting glioma growth. Additionally, glioma patients in the TCGA cohort with high necroptosis gene expression exhibited a better response to ICI therapy predicted by the TIDE algorithm.ConclusionWe constructed a necroptosis gene signature, which has the potential for use as a biomarker for predicting glioma patients’ prognosis, revealing the association between necroptosis and the immune microenvironment, and serving as a reference for immune therapy. |
| first_indexed | 2024-04-13T22:33:45Z |
| format | Article |
| id | doaj.art-b71caed71a3848a98b895d705160f8fa |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T22:33:45Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b71caed71a3848a98b895d705160f8fa2022-12-22T02:26:51ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.855434855434Clinical and Biological Significance of a Necroptosis-Related Gene Signature in GliomaZunjie ZhouJing XuNing HuangJun TangPing MaYuan ChengBackgroundAs a novel form of programmed cell death, necroptosis is related to multiple tumor types and their immune microenvironments. However, its association with glioma has not been clarified.MethodsNecroptosis genes were obtained from the Gene Set Enrichment Analysis (GSEA) database. RNA-seq and clinical data were downloaded from TCGA and CGGA databases. A necroptosis gene signature was constructed based on univariate and multivariate Cox regression analyses. Next, survival analysis, independent prognostic analysis, and nomogram were performed to assess and verify the model. Subsequently, we analyzed the tumor microenvironment (TME) and immune cell infiltration via ESTIMATE and CIBERSORTx algorithms. Finally, the response of glioma patients in the TCGA database to immune checkpoint inhibitor (ICI) therapy was predicted using the Tumor Immune Dysfunction and Exclusion (TIDE) database.ResultsOf the seven prognostic necroptosis genes, RIPK1, RIPK3, FAS, and FADD were used to construct the risk signature that accurately predicts the prognosis of glioma patients. Functional enrichment results suggest that necroptosis is correlated with immune response and angiogenesis. Immune analysis revealed that necroptosis can boost inflammatory activity and attract immunosuppressive cell infiltration to form a chronic inflammatory microenvironment, promoting glioma growth. Additionally, glioma patients in the TCGA cohort with high necroptosis gene expression exhibited a better response to ICI therapy predicted by the TIDE algorithm.ConclusionWe constructed a necroptosis gene signature, which has the potential for use as a biomarker for predicting glioma patients’ prognosis, revealing the association between necroptosis and the immune microenvironment, and serving as a reference for immune therapy.https://www.frontiersin.org/articles/10.3389/fonc.2022.855434/fullnecroptosisprognosisgliomastumor microenvironmentsignatureimmune infiltration |
| spellingShingle | Zunjie Zhou Jing Xu Ning Huang Jun Tang Ping Ma Yuan Cheng Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma Frontiers in Oncology necroptosis prognosis gliomas tumor microenvironment signature immune infiltration |
| title | Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma |
| title_full | Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma |
| title_fullStr | Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma |
| title_full_unstemmed | Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma |
| title_short | Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma |
| title_sort | clinical and biological significance of a necroptosis related gene signature in glioma |
| topic | necroptosis prognosis gliomas tumor microenvironment signature immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.855434/full |
| work_keys_str_mv | AT zunjiezhou clinicalandbiologicalsignificanceofanecroptosisrelatedgenesignatureinglioma AT jingxu clinicalandbiologicalsignificanceofanecroptosisrelatedgenesignatureinglioma AT ninghuang clinicalandbiologicalsignificanceofanecroptosisrelatedgenesignatureinglioma AT juntang clinicalandbiologicalsignificanceofanecroptosisrelatedgenesignatureinglioma AT pingma clinicalandbiologicalsignificanceofanecroptosisrelatedgenesignatureinglioma AT yuancheng clinicalandbiologicalsignificanceofanecroptosisrelatedgenesignatureinglioma |