胶质瘤中人类巨细胞病毒与异柠檬酸脱氢酶状态：摩洛哥人群中的关联及预后价值
Human cytomegalovirus and isocitrate dehydrogenase status in glioma: association and prognosis value in Moroccan population.
作者信息
Fall Coumba, Faiz Mohammed Chaoui El, Hammass Nawal, Fatemi Hinde El, Hassouni Khalid, Bouguenouch Laila, Fakir Samira El, Bennani Bahia
机构信息
PhD student, Laboratory of Human Pathology, Biomedicine and Environment, Faculty of Medicine and Pharmacy Fez, Sidi Mohammed Ben Abdellah University, Sidi Harazem Road, Fez, 30070, Morocco.
MD, Head of the Department of Neurosurgery, Hassan II University Hospital Center, Sidi Harazem Road, Fez, 30070, Morocco.
出版信息
Germs. 2022 Mar 31;12(1):32-45. doi: 10.18683/germs.2022.1304. eCollection 2022 Mar.
INTRODUCTION
Human cytomegalovirus (HCMV) and isocitrate dehydrogenase (IDH) have been separately associated to gliomas. IDH is a molecular marker considered in the histo-molecular classification of gliomas as well as in their management and prognosis. However, even if oncomodulatory properties were attributed to HCMV, its association to gliomas remains a controversy. Most of the studies that investigated this association used the histological classification of gliomas; nevertheless, in 2016, the World Health Organization recommended the introduction of molecular characteristics to refine this classification. The aims of this study were to determine the prevalence of HCMV in glioma patients, the association between HCMV and IDH with gliomas and subsequently their associations with survival of patients in a Moroccan cohort.
METHODS
A series of 102 gliomas and 32 controls were analyzed by nested PCR (nPCR) to determine the HCMV status. PCR and sequencing were used to determine the IDH subtypes in tumors samples. IDH mutation and HCMV status were correlated to the characteristics of the tumors using SPSS, whereas the survival curves were obtained by the Kaplan-Meier method and the log rank test.
RESULTS
HCMV shows significant association with gliomas with a detection rate of 30.4% and no case in the control group. The IDH mutation was identified in 40.9-50% of grade II-III gliomas and in 10.9% of grade IV gliomas. A significant association was obtained between survival in patients with glioblastomas and IDH/HCMV status. Glioblastoma patients with HCMV+ and IDHwt had a poor prognostic.
CONCLUSIONS
HCMV was detected exclusively in tumor cases and was significantly associated with poor prognosis in patients with gliomas and particularly with glioblastomas. The worst overall survival was significantly seen in patients with gliomas HCMV+/IDHwt. So, it will be of interest to consider HCMV and IDH status in gliomas management strategies.
引言
人巨细胞病毒（HCMV）和异柠檬酸脱氢酶（IDH）已分别与胶质瘤相关联。IDH是一种分子标志物，在胶质瘤的组织分子分类以及其治疗和预后评估中都有考量。然而，即使HCMV具有肿瘤调节特性，其与胶质瘤的关联仍存在争议。大多数研究这种关联的研究使用的是胶质瘤的组织学分类；尽管如此，2016年世界卫生组织建议引入分子特征以完善这一分类。本研究的目的是确定摩洛哥队列中胶质瘤患者HCMV的患病率、HCMV和IDH与胶质瘤的关联，以及它们随后与患者生存的关联。
方法
通过巢式PCR（nPCR）分析了102例胶质瘤和32例对照，以确定HCMV状态。采用PCR和测序来确定肿瘤样本中的IDH亚型。使用SPSS将IDH突变和HCMV状态与肿瘤特征相关联，而生存曲线则通过Kaplan-Meier方法和对数秩检验获得。
结果
HCMV与胶质瘤有显著关联，检测率为30.4%，对照组未检测到病例。在II - III级胶质瘤中，IDH突变的检出率为40.9% - 50%，在IV级胶质瘤中为10.9%。胶质母细胞瘤患者的生存与IDH/HCMV状态之间存在显著关联。HCMV阳性且IDH野生型的胶质母细胞瘤患者预后较差。
结论
HCMV仅在肿瘤病例中检测到，与胶质瘤患者尤其是胶质母细胞瘤患者的不良预后显著相关。HCMV阳性/IDH野生型的胶质瘤患者总体生存率最差。因此，在胶质瘤管理策略中考虑HCMV和IDH状态将是有意义的。
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