Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization
Abstract Purpose The 2021 WHO classification of central nervous system tumors introduced molecular criteria to stratify Grade 4 gliomas, which remain heterogeneous. This study aims to elucidate the clinical, radiological, and molecular characteristics of WHO Grade 4 gliomas, focusing on their progno...
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| Format: | Article |
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Springer
2025-02-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-01811-0 |
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| author | Haihui Jiang Xijie Wang Xiaodong Chen Shouzan Zhang Qingsen Ren Mingxiao Li Ming Li Xiaohui Ren Song Lin Yong Cui |
| author_facet | Haihui Jiang Xijie Wang Xiaodong Chen Shouzan Zhang Qingsen Ren Mingxiao Li Ming Li Xiaohui Ren Song Lin Yong Cui |
| author_sort | Haihui Jiang |
| collection | DOAJ |
| description | Abstract Purpose The 2021 WHO classification of central nervous system tumors introduced molecular criteria to stratify Grade 4 gliomas, which remain heterogeneous. This study aims to elucidate the clinical, radiological, and molecular characteristics of WHO Grade 4 gliomas, focusing on their prognostic implications and the development of a predictive model for astrocytoma IDH-mutant WHO Grade 4 (A4). Methods A retrospective cohort of 223 patients from Beijing Tiantan Hospital was analyzed. Clinical, radiological, and histopathological data were combined with molecular profiling, focusing on IDH mutations, TERT promoter mutations, and MGMT methylation. A predictive model was developed using LASSO regression to distinguish A4 from glioblastomas and validated with an external dataset from UCSF. Results The cohort included 201 glioblastomas (90.1%) and 22 A4 cases (9.9%). A4 tumors were associated with younger age, higher MGMT promoter methylation, lower rates of TERT mutations, and distinct radiological features, such as cortical non-enhancing tumor infiltration (CnCE). Patients with A4 demonstrated significantly better survival outcomes compared to glioblastoma patients (p < 0.001). The predictive model for A4, incorporating age, tumor margin, and CnCE, achieved an AUC of 0.890 in the training set and 0.951 in the validation set. Conclusion Integrating molecular and clinical criteria improves prognostication in Grade 4 gliomas. The predictive model developed in this study effectively identifies A4 tumors, facilitating more personalized therapeutic strategies. |
| format | Article |
| id | doaj-art-6fb2e093ecad4a86a7a551499ee14d2f |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-6fb2e093ecad4a86a7a551499ee14d2f2025-02-09T12:43:30ZengSpringerDiscover Oncology2730-60112025-02-0116111410.1007/s12672-025-01811-0Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterizationHaihui Jiang0Xijie Wang1Xiaodong Chen2Shouzan Zhang3Qingsen Ren4Mingxiao Li5Ming Li6Xiaohui Ren7Song Lin8Yong Cui9Department of Neurosurgery, Peking University Third Hospital, Peking UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Peking University Third Hospital, Peking UniversityDepartment of Neurosurgery, Peking University Third Hospital, Peking UniversityDepartment of Neurosurgery, Peking University Third Hospital, Peking UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Purpose The 2021 WHO classification of central nervous system tumors introduced molecular criteria to stratify Grade 4 gliomas, which remain heterogeneous. This study aims to elucidate the clinical, radiological, and molecular characteristics of WHO Grade 4 gliomas, focusing on their prognostic implications and the development of a predictive model for astrocytoma IDH-mutant WHO Grade 4 (A4). Methods A retrospective cohort of 223 patients from Beijing Tiantan Hospital was analyzed. Clinical, radiological, and histopathological data were combined with molecular profiling, focusing on IDH mutations, TERT promoter mutations, and MGMT methylation. A predictive model was developed using LASSO regression to distinguish A4 from glioblastomas and validated with an external dataset from UCSF. Results The cohort included 201 glioblastomas (90.1%) and 22 A4 cases (9.9%). A4 tumors were associated with younger age, higher MGMT promoter methylation, lower rates of TERT mutations, and distinct radiological features, such as cortical non-enhancing tumor infiltration (CnCE). Patients with A4 demonstrated significantly better survival outcomes compared to glioblastoma patients (p < 0.001). The predictive model for A4, incorporating age, tumor margin, and CnCE, achieved an AUC of 0.890 in the training set and 0.951 in the validation set. Conclusion Integrating molecular and clinical criteria improves prognostication in Grade 4 gliomas. The predictive model developed in this study effectively identifies A4 tumors, facilitating more personalized therapeutic strategies.https://doi.org/10.1007/s12672-025-01811-0Molecular pathologyGlioblastomaWHO CNS 5PrognosisPredictive marker |
| spellingShingle | Haihui Jiang Xijie Wang Xiaodong Chen Shouzan Zhang Qingsen Ren Mingxiao Li Ming Li Xiaohui Ren Song Lin Yong Cui Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization Discover Oncology Molecular pathology Glioblastoma WHO CNS 5 Prognosis Predictive marker |
| title | Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization |
| title_full | Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization |
| title_fullStr | Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization |
| title_full_unstemmed | Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization |
| title_short | Unraveling the heterogeneity of WHO grade 4 gliomas: insights from clinical, imaging, and molecular characterization |
| title_sort | unraveling the heterogeneity of who grade 4 gliomas insights from clinical imaging and molecular characterization |
| topic | Molecular pathology Glioblastoma WHO CNS 5 Prognosis Predictive marker |
| url | https://doi.org/10.1007/s12672-025-01811-0 |
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