High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis
Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), is the most malignant brain tumor in adults, with limited therapeutic intervention. Previous studies have identified a few prognostic markers for GBM, including the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promot...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S147655862400157X |
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| author | Soon Sang Park Tae Hoon Roh Yoshiaki Tanaka Young Hwa Kim So Hyun Park Tae-Gyu Kim So Yeong Eom Tae Jun Park In-Hyun Park Se-Hyuk Kim Jang-Hee Kim |
| author_facet | Soon Sang Park Tae Hoon Roh Yoshiaki Tanaka Young Hwa Kim So Hyun Park Tae-Gyu Kim So Yeong Eom Tae Jun Park In-Hyun Park Se-Hyuk Kim Jang-Hee Kim |
| author_sort | Soon Sang Park |
| collection | DOAJ |
| description | Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), is the most malignant brain tumor in adults, with limited therapeutic intervention. Previous studies have identified a few prognostic markers for GBM, including the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter, TERT promoter mutation, EGFR amplification, and CDKN2A/2B deletion. However, the classification of GBM remains incomplete, necessitating a comprehensive analysis. In this study, we investigated the impact of p16INK4A expression in GBM and found that p16INK4A-high GBM exhibits distinct characteristics compared to p16INK4A-low GBM. Specifically, tumor cells with p16INK4A-high expression display a senescent phenotype and are correlated with higher intra-tumoral immune cell infiltration. Furthermore, an association was observed between elevated p16INK4A expression in GBM and extended overall survival of patients. Our in vivo and in vitro studies revealed that CCL13 is predominantly expressed by p16INK4A-high GBM cells. The released CCL13 enhances the infiltration of T cells within the tumor, potentially contributing to the improved prognosis observed in patients with high p16INK4A expression. These findings suggest that tumor cells with a senescence phenotype in GBM, through the secretion of chemokines such as CCL13, may augment immune cell infiltration and potentially enhance patient outcomes by creating a more immunologically active tumor microenvironment. |
| format | Article |
| id | doaj-art-ae433d2d3dc04eb6a70db8d1791e515a |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-ae433d2d3dc04eb6a70db8d1791e515a2025-02-03T04:16:35ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-02-0160101116High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosisSoon Sang Park0Tae Hoon Roh1Yoshiaki Tanaka2Young Hwa Kim3So Hyun Park4Tae-Gyu Kim5So Yeong Eom6Tae Jun Park7In-Hyun Park8Se-Hyuk Kim9Jang-Hee Kim10Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Republic of Korea; Inflammaging Translational Research Center, Ajou University Hospital, Suwon 16499, Republic of KoreaDepartment of Neurosurgery, Ajou University School of Medicine, Suwon 16499, Republic of KoreaMaisonneuve-Rosemont Hospital Research Center, Department of Medicine, University of Montreal, H1T2M4 CanadaInflammaging Translational Research Center, Ajou University Hospital, Suwon 16499, Republic of Korea; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaInflammaging Translational Research Center, Ajou University Hospital, Suwon 16499, Republic of Korea; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaInflammaging Translational Research Center, Ajou University Hospital, Suwon 16499, Republic of Korea; Department of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of KoreaDepartment of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Republic of Korea; Inflammaging Translational Research Center, Ajou University Hospital, Suwon 16499, Republic of KoreaDepartment of Genetics, Yale Stem Cell Center, Yale Child Study Center, Yale School of Medicine, New Haven 06520, USADepartment of Neurosurgery, Ajou University School of Medicine, Suwon 16499, Republic of Korea; Corresponding author at: Department of Neurosurgery, Ajou University School of Medicine, Suwon, Republic of Korea.Department of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of Korea; Corresponding author at: Department of Pathology, Ajou University School of Medicine, Suwon 16499, Republic of Korea.Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), is the most malignant brain tumor in adults, with limited therapeutic intervention. Previous studies have identified a few prognostic markers for GBM, including the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter, TERT promoter mutation, EGFR amplification, and CDKN2A/2B deletion. However, the classification of GBM remains incomplete, necessitating a comprehensive analysis. In this study, we investigated the impact of p16INK4A expression in GBM and found that p16INK4A-high GBM exhibits distinct characteristics compared to p16INK4A-low GBM. Specifically, tumor cells with p16INK4A-high expression display a senescent phenotype and are correlated with higher intra-tumoral immune cell infiltration. Furthermore, an association was observed between elevated p16INK4A expression in GBM and extended overall survival of patients. Our in vivo and in vitro studies revealed that CCL13 is predominantly expressed by p16INK4A-high GBM cells. The released CCL13 enhances the infiltration of T cells within the tumor, potentially contributing to the improved prognosis observed in patients with high p16INK4A expression. These findings suggest that tumor cells with a senescence phenotype in GBM, through the secretion of chemokines such as CCL13, may augment immune cell infiltration and potentially enhance patient outcomes by creating a more immunologically active tumor microenvironment.http://www.sciencedirect.com/science/article/pii/S147655862400157XGlioblastomaGBM IDH-wildtypeSenescenceSenescent tumor cellsCCL13 |
| spellingShingle | Soon Sang Park Tae Hoon Roh Yoshiaki Tanaka Young Hwa Kim So Hyun Park Tae-Gyu Kim So Yeong Eom Tae Jun Park In-Hyun Park Se-Hyuk Kim Jang-Hee Kim High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis Neoplasia: An International Journal for Oncology Research Glioblastoma GBM IDH-wildtype Senescence Senescent tumor cells CCL13 |
| title | High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis |
| title_full | High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis |
| title_fullStr | High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis |
| title_full_unstemmed | High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis |
| title_short | High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis |
| title_sort | high p16ink4a expression in glioblastoma is associated with senescence phenotype and better prognosis |
| topic | Glioblastoma GBM IDH-wildtype Senescence Senescent tumor cells CCL13 |
| url | http://www.sciencedirect.com/science/article/pii/S147655862400157X |
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