The TERT promoter mutation status and MGMT promoter methylation status, combined with dichotomized MRI‐derived and clinical features, predict adult primary glioblastoma survival

Abstract

PurposeThis study aimed to integrate the TERT promoter mutation status, MGMT promoter methylation status, MRI‐derived features, and clinical features into a survival analysis model to better understand adult primary glioblastoma prognosis‐related markers.MethodA total of 304 adult glioblastoma samples collected after surgical resection were selected for retrospective analysis, and Sanger sequencing was performed to detect IDH and TERT promoter mutations. The methylation of the MGMT promoter was analyzed by pyrosequencing, and MRI‐derived and clinical features were dichotomized into easily acquired variables. Random survival forest analysis, Kaplan‐Meier analysis, Cox proportional hazard regression, and LASSO regression were performed for the survival analysis, and ROC analysis and Pearson's chi‐squared test were employed for the correlation analysis.ResultsWild‐type IDH was present in 89.8% of the adult glioblastoma samples, and TERT promoter mutations and MGMT promoter methylation were observed in 66.42% and 38.49% of all adult primary glioblastomas, respectively. Age and MGMT promoter methylation were identified as independent prognostic biomarkers, and the TERT promoter mutation status and MGMT promoter methylation status, when combined with other tumor‐related factors, generated several different survival subgroups. None of the factors investigated in this study predicted the MGMT promoter status, and MRI‐detected necrosis was positively associated with TERT promoter mutations.ConclusionMGMT promoter methylation and TERT promoter mutations, combined with MRI‐derived and clinical features, revealed different survival subgroups with distinct responses to current treatments, and this information increases the ability to predict the survival of adult primary glioblastoma patients. MRI‐detected necrosis often indicates the presence of TERT promoter mutations.

The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

“…Mutation of TERT promoter as a genetic event is frequently detected in 60-75% of glioblastomas (GBM), and associated with a poor prognosis [5,6]. While TERT promoter mutation showed a poor survival prognosis in glioma patients, O 6 -methylguanine-DNA methyltransferase (MGMT) methylation has long been recognized as an important factor in treatment decisions [7], and is also a positive prognostic factor [8][9][10][11][12]. Our previous study, along with others, indicated that the prognostic value of TERT promoter mutation in gliomas is influenced by the status of IDH mutations [5,[13][14][15].…”

The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

“…In one recent study, the TERT-mut/MGMT-unmeth GBM was associated with worse magnetic resonant imaging (MRI) characteristics such as low apparent diffusion coe cient values, obvious edema, obvious necrosis, unobvious non-contrast enhancing tumor, deep white matter invasion, and a high Ki-67 labeling rather than other groups. [49] On the other hand, it is interesting to note that TERT promoter mutation is an independent prognostic marker in other cancers (e.g., melanoma, thyroid cancer, urothelial carcinoma) and is not in uenced by other mutations such as RAS or BRAF mutations [44,45,[50][51][52]. In gliomas, the prognostic impact of TERT promoter mutation has been known to be modulated by IDH mutations [13].…”

“…Mutation of TERT promoter as a genetic event is frequently detected in 60-75% of glioblastomas (GBM), and associated with a poor prognosis [5,6]. While TERT promoter mutation showed a poor survival prognosis in glioma patients, O 6 -methylguanine-DNA methyltransferase (MGMT) methylation has long been recognized as an important factor in treatment decisions [7], and is also a positive prognostic factor [8][9][10][11][12]. Our previous study, along with others, indicated that the prognostic value of TERT promoter mutation in gliomas is in uenced by the status of IDH mutations [5,[13][14][15].…”

“…The prognostic inter-relationship between TERT promoter mutations and MGMT methylation status has been unclear. The combination of TERT promoter mutations and MGMT promoter methylation has de ned subgroups with noticeable responses to current treatments [10]. Some data have suggested that glioblastoma patients harboring MGMT methylation have a different prognosis depending on TERT promoter mutation status [16]; on the other hand, some studies have reported no association in the cooccurrence of TERT promoter mutation and MGMT methylation in glioma patients [14,[17][18][19].…”

Integrative Analysis of Histopathological Images and Genomic Data in Colon Adenocarcinoma

“…[18,39] Some has also found that integrating models can improve prediction power by combining genes and images such as magnetic resonance imaging and computerized tomography. [40][41][42] On account of the changes in cancer genetic mechanisms are often re ected in cell morphology, pathological images have better insight into other medical images.…”