STING is significantly increased in high-grade glioma with high risk of recurrence
In this study, we aimed to comprehensively characterize the potential relationships among the frequently mutated genes, well-known homologous recombination repair (HRR) proteins, and immune proteins in glioma from a clinical perspective. A total of 126 surgical tissues from patients initially diagno...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2327682 |
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| author | Meishi Zhong Manmei Long Chenjie Han Saiyan Ji Qingyuan Yang |
| author_facet | Meishi Zhong Manmei Long Chenjie Han Saiyan Ji Qingyuan Yang |
| author_sort | Meishi Zhong |
| collection | DOAJ |
| description | In this study, we aimed to comprehensively characterize the potential relationships among the frequently mutated genes, well-known homologous recombination repair (HRR) proteins, and immune proteins in glioma from a clinical perspective. A total of 126 surgical tissues from patients initially diagnosed with glioma were included. The genetic alterations were tested using the targeted next-generation sequencing technique. The expression of HRR proteins, immune proteins, and genetic alteration-related proteins were detected using immunostaining. Integrated analysis showed that ATRX is positively correlated with STING in high-grade glioma (HGG) with wild-type ATRX and IDH1. Then, a relapse predictive risk-scoring model was established using the least absolute shrinkage and selection operator regression algorithms. The scores based on the expression of ATRX and STING significantly predict the recurrence for glioma patients, which further predict the survival for specific subgroups, characterized with high expression of RAD51 and wild-type TERT. Moreover, STING is significantly higher in patients with high relapse risk. Interestingly, STING inhibitors and agonists both suppress the growth of HGG cells, regardless of their STING levels and STING pathway activity, whereas RAD51 inhibitor B02 is found to exclusively sensitize HGG cells with high expression of STING to temozolomide in vitro and in vivo. Overall, findings in the study not only reveal that ATRX is closely correlated with STING to drive the relapse of HGG, but also provide a STING-guided combined strategy to treat patients with aggressive gliomas. Translation of these findings will ultimately improve the outcomes for ATRX and IDH1 genomically stratified subgroups in HGG. |
| format | Article |
| id | doaj-art-9d6432bba87449a18fb9b220cc6b5ecd |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | OncoImmunology |
| spelling | doaj-art-9d6432bba87449a18fb9b220cc6b5ecd2025-08-20T02:50:37ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2327682STING is significantly increased in high-grade glioma with high risk of recurrenceMeishi Zhong0Manmei Long1Chenjie Han2Saiyan Ji3Qingyuan Yang4Department of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaIn this study, we aimed to comprehensively characterize the potential relationships among the frequently mutated genes, well-known homologous recombination repair (HRR) proteins, and immune proteins in glioma from a clinical perspective. A total of 126 surgical tissues from patients initially diagnosed with glioma were included. The genetic alterations were tested using the targeted next-generation sequencing technique. The expression of HRR proteins, immune proteins, and genetic alteration-related proteins were detected using immunostaining. Integrated analysis showed that ATRX is positively correlated with STING in high-grade glioma (HGG) with wild-type ATRX and IDH1. Then, a relapse predictive risk-scoring model was established using the least absolute shrinkage and selection operator regression algorithms. The scores based on the expression of ATRX and STING significantly predict the recurrence for glioma patients, which further predict the survival for specific subgroups, characterized with high expression of RAD51 and wild-type TERT. Moreover, STING is significantly higher in patients with high relapse risk. Interestingly, STING inhibitors and agonists both suppress the growth of HGG cells, regardless of their STING levels and STING pathway activity, whereas RAD51 inhibitor B02 is found to exclusively sensitize HGG cells with high expression of STING to temozolomide in vitro and in vivo. Overall, findings in the study not only reveal that ATRX is closely correlated with STING to drive the relapse of HGG, but also provide a STING-guided combined strategy to treat patients with aggressive gliomas. Translation of these findings will ultimately improve the outcomes for ATRX and IDH1 genomically stratified subgroups in HGG.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2327682ATRXhigh-grade gliomaIDH1RAD51 inhibitorSTINGtemozolomide sensitivity |
| spellingShingle | Meishi Zhong Manmei Long Chenjie Han Saiyan Ji Qingyuan Yang STING is significantly increased in high-grade glioma with high risk of recurrence OncoImmunology ATRX high-grade glioma IDH1 RAD51 inhibitor STING temozolomide sensitivity |
| title | STING is significantly increased in high-grade glioma with high risk of recurrence |
| title_full | STING is significantly increased in high-grade glioma with high risk of recurrence |
| title_fullStr | STING is significantly increased in high-grade glioma with high risk of recurrence |
| title_full_unstemmed | STING is significantly increased in high-grade glioma with high risk of recurrence |
| title_short | STING is significantly increased in high-grade glioma with high risk of recurrence |
| title_sort | sting is significantly increased in high grade glioma with high risk of recurrence |
| topic | ATRX high-grade glioma IDH1 RAD51 inhibitor STING temozolomide sensitivity |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2327682 |
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