Immunohistochemical Expression of IDH1, ATRX, Ki67, GFAP, and Prognosis in Indonesian Glioma Patients

Priambada, Dody; Arifin, Muhamad Thohar; Saputro, Abdi; Muzakka, Azka; Karlowee, Vega; Sadhana, Udadi; Bakhtiar, Yuriz; Prihastomo, Krisna Tsaniadi; Risdianto, Ajid; Brotoarianto, Happy Kurnia; Andar, Erie Bps; Muttaqin, Zainal

doi:10.2147/ijgm.s397550

Cited by 6 publications

(3 citation statements)

References 19 publications

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“…Individuals with IDH1 mutations had better outcomes than those without. 44 Consistent with this, we observed that the FS1 patients, who experienced the worst prognosis, did not exhibit any IDH1 mutations. Next, the assessment of the relationship between F-subtypes and TIME was performed.…”

Section: Dovepresssupporting

confidence: 87%

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

Zhao,

Xing,

Guo

et al. 2024

PGPM

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mRNA vaccines represent a promising and innovative strategy within the realm of cancer immunotherapy. However, their efficacy in treating lower-grade glioma (LGG) requires evaluation. Ferroptosis exhibits close associations with the initiation, evolution, and suppression of cancer. In this study, we explored the landscape of the ferroptosis-associated tumor microenvironment to facilitate the development of mRNA vaccines for LGG patients. Patients and Methods: Genomic and clinical data of the LGG patients was obtained from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Ferroptosis-related tumor antigens were identified based on differential expression, mutation status, correlation with antigen-presenting cells, and prognosis, relevance to immunogenic cell death (ICD). Antigen expression levels in LGG specimens and cell lines were validated using real time-polymerase chain reaction (RT-PCR). Consensus clustering was employed for patient classification. The immune landscapes of ferroptosis subtypes were further characterized, including immune responses, prognostic ability, tumor microenvironment, and tumor-related signatures. Results: Five tumor antigens, namely, HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified in LGG. RT-PCR demonstrated higher expression of these genes in LGG compared to the control. Twelve gene modules and four ferroptosis subtypes (FS1-FS4) of LGG were defined. FS2 and FS4, characterized as "cold" tumors due to their decreased tumor mutation burden (TMB) and immune checkpoint proteins (ICPs), were deemed appropriate candidates for the mRNA vaccine. Conclusion: HOTAIR, IDO1, KIF20A, NR5A2, and RRM2 were identified as promising candidate antigens for the development of an LGG mRNA vaccine, particularly offering potential benefits to FS2 and FS4 patients.

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Section: Dovepresssupporting

confidence: 87%

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

Zhao,

Xing,

Guo

et al. 2024

PGPM

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“…Regarding gender distribution, Jakovlevs A observed a slight predominance of females (51.4%), which is in contrast to our study, where the males were more frequently affected by these malignant lesions [23]. Similar to our study, Priambada et [25,26,28,29]. In the study by Alimohammadi E et al, in over 60% of the analysed group, glioblastomas predominantly affected the male sex, and almost 10% of them were IDH-1 mutant glioblastomas [32].…”

Section: Discussionsupporting

confidence: 73%

General Clinico-Pathological Characteristics in Glioblastomas in Correlation with p53 and Ki67

Sipos,

Kövecsi,

Ovidiu-Ioan

et al. 2023

Medicina

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Introduction: A glioblastoma is an intra-axial brain tumour of glial origin that belongs to the category of diffuse gliomas and is the most common malignant neoplasia of the central nervous system. The rate of survival at 5 years, from the moment of diagnosis, is not higher than 10%. Materials and methods: In this retrospective study, fifty-four patients diagnosed with glioblastoma, from the Pathology Department of the County Emergency Clinical Hospital of Târgu Mureș, between 2014 and 2017 were included. We studied the clinico-pathological data (age, gender, location, and laterality) and, respectively, the immunoexpression of p53, Ki67, ATRX, and IDH-1 proteins. Results: We observed a statistically significant association between the laterality of the tumour according to the age groups, with the localization on the right side being more frequent in the age group below 65 years of age, while the involvement of the left hemisphere was more prevalent in those over 65 years. Out of the total 54 cases, 87.04% were found to be primary glioblastomas; more than 70% of the cases were ATRX immunopositive; almost 80% of the glioblastomas studied had wild-type p53 profile; and 35% of the cases were found to have a Ki67 index greater than 20%. A statistically significant association between gender and ATRX mutation was found; female cases were ATRX immunopositive in 92% of the cases. Almost 70% of the cases were both IDH-1 and p53 wild-type, and we observed the presence of both mutations in only 3.7% of the cases. Approximately 83% of primary glioblastomas were ATRX positive, respectively, and all IDH-1 mutant cases were ATRX negative. Conclusions: Glioblastomas still represent a multidisciplinary challenge considering their reserved prognosis. In this study, we described the most common clinico-pathological characteristics and IHC marker expression profiles, highlighting a variety of percentage ranges in primary and secondary glioblastomas. Given the small number of studied cases, further prospective studies on larger cohorts are needed in the future to evaluate the role of these immunohistochemical markers as prognostic factors for survival or recurrence.

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“…The ATRX mutations occurs at high frequencies in both low-grade gliomas (71%) and secondary GBM (57%) [ 14 ]. Isocitrate dehydrogenase (IDH) mutant GBM with ATRX loss exhibits a higher survival rate than the IDH mutant with the wild-type ATRX gene [ 15 ]. ATRX is a chromatin remodeling protein that plays an important role in the deposition of the histone variant H3.3 [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of ATRX enhances radiosensitivity in glioblastoma

Zhao,

Chen,

Liu

et al. 2024

Chin Neurosurg Jl

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Background Glioblastoma are highly malignant type of primary brain tumors. Treatment for glioblastoma multiforme (GBM) generally involves surgery combined with chemotherapy and radiotherapy. However, the development of tumoral chemo- and radioresistance induces complexities in clinical practice. Multiple signaling pathways are known to be involved in radiation-induced cell survival. However, the role of alpha-thalassemia X-linked mutant retardation syndrome (ATRX), a chromatin remodeling protein, in GBM radioresistance remains unclear. Methods In the present study, the ATRX mutation rate in patients with glioma was obtained from The Cancer Genome Atlas, while its expression analyzed using bioinformatics. Datasets were also obtained from the Gene Expression Omnibus, and ATRX expression levels following irradiation of GBM were determined. The effects of ATRX on radiosensitivity were investigated using a knockdown assays. Results The present study demonstrated that the ATRX mutation rate in patients with GBM was significantly lower than that in patients with low-grade glioma, and that patients harboring an ATRX mutation exhibited a prolonged survival, compared with to those harboring the wild-type gene. Single-cell RNA sequencing demonstrated that ATRX counts increased 2 days after irradiation, with ATRX expression levels also increasing in U-251MG radioresistant cells. Moreover, the results of in vitro irradiation assays revealed that ATRX expression was increased in U-251MG cells, while ATRX knockdown was associated with increased levels of radiosensitivity. Conclusions High ATRX expression levels in primary GBM may contribute to high levels of radioresistance. Thus ATRX is a potential target for overcoming the radioresistance in GBM.

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Immunohistochemical Expression of IDH1, ATRX, Ki67, GFAP, and Prognosis in Indonesian Glioma Patients

Cited by 6 publications

References 19 publications

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

Identification of Lower Grade Glioma Antigens Based on Ferroptosis Status for mRNA Vaccine Development

General Clinico-Pathological Characteristics in Glioblastomas in Correlation with p53 and Ki67

Knockdown of ATRX enhances radiosensitivity in glioblastoma

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