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Tumor suppressor (p53) acts to integrate multiple stress signals into diverse antiproliferative responses. Its potential to transactivate or downregulate genes through apoptotic pathway in IDH-wildtype glioblastoma has never been explored. A group of twenty patients diagnosed with IDH-wildtype glioblastoma, were tested for p53 expression and NDRG2/NRF2 genes activity through protein and gene profiling assays. The connotation between these elements has been explored. The mean patients' age was 64-years. All tumors were IDH-wildtype. p53 was expressed in 12 tumors and absent in 8 tumors. The activity of NDRG2 gene was downregulated in all cases. The activity of NRF2 gene was upregulated in 17 tumors and downregulated in 3 tumors. There was a significant statistical difference in PFS among tumors exhibiting different levels of p53 expression and NDRG2 gene activity [p-value= 0.025], in which 12 tumors with downregulated NDRG2 expression and positive p53 expression had earlier tumor recurrence. This statistical difference in PFS was insignificant when we compared p53 expression with NRF2 gene activity [p-value= 0.079]. During cell cycle arrest at G2 phase, p53 expression in IDH-wildtype glioblastoma in elderly individuals, coupled with the downregulation of NDRG2 gene activity, led to an aberrant increase in tumor cell proliferation and accelerated tumor recurrence. However, the influence of p53 on NRF2 gene activity was found to be insignificant. [ABSTRACT FROM AUTHOR]

Purpose: Wilms tumor 1 ( WT1 ) gene has recently shown a role in gliomagenesis, making it a potential immunotherapy target in glioblastomas. We aimed to investigate the most sensitive method to detect WT1 expression in glioblastoma and explore the relationship between WT1 expression, IDH1 mutation and recurrence interval., Patients and Methods: Clinical data were collected from 44 patients with glioblastomas, treated with adjuvant therapies. WT1 expression was assessed in all cases using immunohistochemistry (IHC), while its gene expression was assessed in 13 clustered samples using polymerase chain reaction (qPCR). IDH1 mutation was assessed using IHC. The sensitivity between IHC and RT-qPCR was examined. Kaplan-Meier curves were used to compare the recurrence-free interval (RFI) between IDH1 and WT1 expression groups., Results: IDH1 wildtype was found in 26 cases (59.1%) and the remaining 18 cases (40.9%) were IDH1 mutant . Through IHC, WT1 was overexpressed in 32 cases (72.7%), partially expressed in 9 cases (20.5%) and not expressed in only 3 cases. For the 13 cases tested by qPCR, 6 cases showed WT1 upregulation and 7 cases showed WT1 downregulation. There was no significant difference in WT1 expression among cases with different RNA concentrations regardless the testing method (p-value >0.05). However, the difference between IHC and qPCR was significant. IDH1 mutant cases with WT1 overexpression showed significant difference in RFI (p-value =0.048)., Conclusion: Parallel testing for WT1 expression using IHC and qPCR is not reliable. However, IHC provides more accurate results. Moreover, IDH1 mutant glioblastomas with WT1 overexpression are associated with late RFI particularly if temozolomide with additional chemotherapies are used., Competing Interests: All authors reported no conflicts of interest for this work., (© 2021 Kurdi et al.)

The aim of this study is to investigate the relationship between isocitrate dehydrogenase-1 ( IDH1 ) mutation and O 6 -methylguanine-DNA methyltransferase ( MGMT ) promoter methylation with recurrence-free interval in glioblastoma patients treated with chemoradiotherapies. Clinical data were collected from 82 patients with totally resected glioblastoma and treated with adjuvant therapies from 2014 to 2019. IDH1 mutation was assessed by immunohistochemistry and MGMT promoter methylation was assessed by different sequencing methods. IDH1 mutation was present in 32 cases and 50 cases were IDH1 wildtype; 54 and 28 patients had unmethylated and methylated MGMT promoter, respectively, Of the 82 patients, 62 patients received chemoradiotherapy while 20 patients only received radiation. Approximately, 61% of patients had a tumor recurrence after 1 year, and 39% showed a recurrence before 1 year of treatment. There was no significant relationship between IDH1 mutation and MGMT promoter methylation ( p -value = 0.972). Patients with IDH1 mutation and their age <50 years showed a significant difference in recurrence-free interval ( p -value = 0.014). Difference in recurrence-free interval was also statistically observed in patients with unmethylated MGMT promoter and treated with chemoradiotherapies ( p -value = 0.031), by which they showed a late tumor recurrence ( p -value = 0.016). This revealed that IDH1 mutation and MGMT methylation are independent prognostic factors in glioblastoma. Although IDH1 -mutant glioblastomas showed late tumor recurrence in patients less than 50 years old, the type of treatment modalities may not show additional beneficial outcome. Patients with unmethylated MGMT and IDH1 mutation, treated with different chemoradiotherapies, showed a late tumor recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kurdi, Shafique Butt, Baeesa, Alghamdi, Maghrabi, Bardeesi, Saeedi, Al-Sinani, Alghanmi, Bari, Samkari and Lary.)