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This document provides a summary of a research study that explores the relationship between IDH mutation, MGMT-promoter methylation, and PRMT5 gene expression in grade 4 astrocytoma. The study found that there is a significant relationship between MGMT-promoter methylation and IDH mutation in these tumors. It also suggests that using a PRMT5 inhibitor may be beneficial in tumor regression. The document also includes a list of references related to glioblastoma, providing valuable information for researchers and individuals interested in studying this type of brain cancer. [Extracted from the article]

Introduction: CD8+ T-cells and MHC-I have been detected in brain gliomas with a significant outcome. The effect of chemotherapies on the crosstalk interaction between CD8+ T-cells and MHC-I has never been explored. Material and methods: The protein expression profiling of CD8 cytotoxic T-cells and the gene expression assay of MHC-I in 35 patients diagnosed with WHO grade 4 astrocytoma were performed. The impact of these two factors on tumor recurrence was analyzed. Results: IDH was wildtype in 13 tumors. MHC-I protein expression was absent or low in 34 tumors and dense in a single case. MHC-I gene expression was upregulated in 10 tumors and 25 tumors showed MHC-I gene downregulation. Temozolomide (TMZ) was given to 24 patients and 11 patients received TMZ plus other chemotherapies. No statistically signifi- cant association was observed between IDH mutation and CD8+ T-cells (p = 0.383). However, this association was significant in recurrence-free interval (RFI) (p = 0.012). IDH-wildtype tumors with highly infiltrated CD8+ T-cells or IDH-mutant tumors with low CD8+ T-cells showed late tumor recurrence. There was a statistically significant difference in RFI between tumors with different MHC-I expression and CD8+ T-cell counts after treatment with TMZ or TMZ plus (p = 0.026). Conclusions: No association between IDH mutation and CD8+ cytotoxic T-cell was found. IDH is directly linked to tumor recurrence regardless of CD8+ T-cells infiltration. TMZ plus other adjuvants is proved to be more effective in improving patient survival and delaying tumor recurrence, as compared to using TMZ alone. Nonetheless, none-TMZ adjuvants may increase tumor sensitization to cytotoxic T-cells more than TMZ. [ABSTRACT FROM AUTHOR]

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]

Augmenting traditional genome-wide association studies (GWAS) with advanced machine learning algorithms can allow the detection of novel signals in available cohorts. We introduce "genome-wide association neural networks (GWANN)" a novel approach that uses neural networks (NNs) to perform a gene-level association study with family history of Alzheimer's disease (AD). In UK Biobank, we defined cases (n = 42 110) as those with AD or family history of AD and sampled an equal number of controls. The data was split into an 80:20 ratio of training and testing samples, and GWANN was trained on the former followed by identifying associated genes using its performance on the latter. Our method identified 18 genes to be associated with family history of AD. APOE, BIN1, SORL1, ADAM10, APH1B, and SPI1 have been identified by previous AD GWAS. Among the 12 new genes, PCDH9, NRG3, ROR1, LINGO2, SMYD3, and LRRC7 have been associated with neurofibrillary tangles or phosphorylated tau in previous studies. Furthermore, there is evidence for differential transcriptomic or proteomic expression between AD and healthy brains for 10 of the 12 new genes. A series of post hoc analyses resulted in a significantly enriched protein-protein interaction network (P-value < 1 × 10-16), and enrichment of relevant disease and biological pathways such as focal adhesion (P-value = 1 × 10-4), extracellular matrix organization (P-value = 1 × 10-4), Hippo signaling (P-value = 7 × 10-4), Alzheimer's disease (P-value = 3 × 10-4), and impaired cognition (P-value = 4 × 10-3). Applying NNs for GWAS illustrates their potential to complement existing algorithms and methods and enable the discovery of new associations without the need to expand existing cohorts., (© The Author(s) 2025. Published by Oxford University Press.)