Characteristic analysis and identification of novel molecular biomarkers in elderly glioblastoma patients using the 2021 WHO Classification of Central Nervous System Tumors

Yaning Wang; Junlin Li; Yaning Cao; Wenlin Chen; Hao Xing; Xiaopeng Guo; Yixin Shi; Yuekun Wang; Tingyu Liang; Liguo Ye; Delin Liu; Tianrui Yang; Yu Wang; Wenbin Ma

doi:10.3389/fnins.2023.1165823

Characteristic analysis and identification of novel molecular biomarkers in elderly glioblastoma patients using the 2021 WHO Classification of Central Nervous System Tumors

Front Neurosci. 2023 Jun 9:17:1165823. doi: 10.3389/fnins.2023.1165823. eCollection 2023.

Authors

Yaning Wang¹, Junlin Li^{1

2}, Yaning Cao^{1

2}, Wenlin Chen¹, Hao Xing¹, Xiaopeng Guo^{1

3}, Yixin Shi^{1

2}, Yuekun Wang¹, Tingyu Liang¹, Liguo Ye¹, Delin Liu^{1

2}, Tianrui Yang^{1

2}, Yu Wang^{1

3}, Wenbin Ma^{1

3}

Affiliations

¹ Department of Neurosurgery, Center for Malignant Brain Tumors, National Glioma MDT Alliance, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Eight-Year Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ China Anti-Cancer Association Specialty Committee of Glioma, Beijing, China.

Abstract

Introduction: Elderly glioblastoma (GBM) patients is characterized by high incidence and poor prognosis. Currently, however, there is still a lack of adequate molecular characterization of elderly GBM patients. The fifth edition of the WHO Classification of Central Nervous System Tumors (WHO5) gives a new classification approach for GBM, and the molecular characteristics of elderly GBM patients need to be investigated under this new framework.

Methods: The clinical and radiological features of patients with different classifications and different ages were compared. Potential prognostic molecular markers in elderly GBM patients under the WHO5 classification were found using Univariate Cox regression and Kaplan-Meier survival analysis.

Results: A total of 226 patients were included in the study. The prognostic differences between younger and elderly GBM patients were more pronounced under the WHO5 classification. Neurological impairment was more common in elderly patients (p = 0.001), while intracranial hypertension (p = 0.034) and epilepsy (p = 0.038) were more common in younger patients. Elderly patients were more likely to have higher Ki-67(p = 0.013), and in elderly WHO5 GBM patients, KMT5B (p = 0.082), KRAS (p = 0.1) and PPM1D (p = 0.055) were each associated with overall survival (OS). Among them, KRAS and PPM1D were found to be prognostic features unique to WHO5 elderly GBM patients.

Conclusion: Our study demonstrates that WHO5 classification can better distinguish the prognosis of elderly and younger GBM. Furthermore, KRAS and PPM1D may be potential prognostic predictors in WHO5 elderly GBM patients. The specific mechanism of these two genes in elderly GBM remains to be further studied.

Keywords: 2021 WHO Classification of Central Nervous System Tumors; KRAS; PPM1D; geriatric; glioblastoma.