scholarly journals Changes of the O6-methylguanine-DNA methyltransferase promoter methylation and MGMT protein expression after adjuvant treatment in glioblastoma

2010 ◽  
Vol 23 (5) ◽  
Author(s):  
Jung
Keyword(s):  
Protein Expression ◽  
Adjuvant Treatment ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Protein

scholarly journals Tim-3 protein expression with MGMT methylation status in glioblastoma and association with survival

2020 ◽  
Author(s):  
ji zhang ◽  
Xiaoli Wang ◽  
Shengquan Ye ◽  
Lijiao Liang ◽  
Yi Zhou ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Methylation ◽  
Immune Checkpoint ◽  
Dna Methyltransferase ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Mgmt Promoter Methylation ◽  
Mgmt Methylation ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Promoter

Abstract Background Understanding the molecular landscape of glioblastoma (GBM) is increasingly crucial for its therapy. Immune checkpoint molecules motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecule T cell immunoglobulin mucin-3 (Tim-3) on tumor-infiltrating immune cells (TIICs) and O-6-Methylguanine-DNA methyltransferase (MGMT) methylation status remains to be fully elucidated. We aimed to develop an MGMT methylation status-associated immune prognostic signature for predicting prognosis in GBMs.Patients and Methods: A total of 84 patients with newly diagnosed GBM were involved. MGMT methylation status was retrospectively analyzed and the expression level of Tim-3 protein was investigated using immunohistochemistry (IHC). The correlation between Tim-3 protein expression and MGMT methylation status, and the prognosis was explored.Results The obtained data showed that Tim-3 protein was expressed at different levels in GBMs. Mesenchymal expression of Tim-3 protein in these tissues was 73.81% (62/84), including low 15.48% (13/84), moderate 7.14% (6/84) and strong expression 51.19% (43/84), respectively. Of the 48 patients whose tumors tested positive for MGMT methylation, the remaining 36 patients was negative.Conclusions We profiled the immune status in GBM with MGMT promoter methylation and established a local immune signature for GBM, which could independently identify patients with a favorable prognosis, indicating the relationship between prognosis and immune. MGMT promoter methylation with lower Tim-3 protein expression was statistically significantly associated with better survival.

Predictive chemotherapy according to O6-methylguanine-DNA methyltransferase protein expression for treatment of malignant gliomas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12530-12530
Author(s):  
Z. Chen ◽  
J. Zhang ◽  
Q. Wu
Keyword(s):  
Protein Expression ◽  
Stable Disease ◽  
Dna Methyltransferase ◽  
Response Rate ◽  
Malignant Gliomas ◽  
Hematological Toxicity ◽  
Chemotherapeutic Regimen ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Protein ◽  
Grade 3

12530 Background: To evaluate the response to predictable chemotherapy according to O6-methylguanine-DNA methyltransferase (MGMT) expression pattern and toxicity in patients with malignant gliomas. Methods: Twenty-eight patients with histologically confirmed malignant gliomas were enrolled in this study. The glioma tissues were examined for MGMT protein expression by immunohistochemistry. The chemotherapeutic regimen wasn’t consisted of nitrosourea or temozolomide in patients with MGMT positive expression, while no limitation using nitrosourea or temozolomide in patients with MGMT negative expression. The patients who received 2 or more than 2 cycles of chemotherapy were evaluated for response to therapy according WHO standard, and toxicity according National Cancer Institute (NCI) standard. Results: Twenty-four patients were used one regimen while 4 patients received two regimens chemotherapy, and thus overall 32 cases were evaluated for response to chemotherapy. The complete response (CR) was observed in 5 cases (16%),partial response (PR) in 6 cases (19%), stable disease (SD) was seen in 12 cases (38%), and 9 cases (28%) developed progressive disease (PD). Objective response rate (CR + PR) was 35%, and response plus stable disease rate (CR+PR+SD) was 73%. Hematological toxicity was the principal limiting side-effect observed in this study. Seven patients (25%, 7/28) experienced grade 3 or 4 leucopenia and one (4%,1/28) grade 4 thrombocytopenia who received platelet transfusion. No hemorrhagic event due to thrombocytopenia occurred. Non- hematological toxicity mainly was nausea/vomiting and alopecia. Grade 3 nausea/vomiting occurred in 7% of patients (2/28) and grade 3 alopecia in 7% of patients (2/28). Conclusions: The predictive chemotherapy according to MGMT protein expression in patients with malignant gliomas could improve overall response rate with acceptable side-effect, as compared with conventional chemotherapeutic regimen, and thus worth for further investigation. No significant financial relationships to disclose.

scholarly journals Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770163 ◽  
Author(s):  
Snigdha Saikia ◽  
Asad Ur Rehman ◽  
Prajjalendra Barooah ◽  
Preeti Sarmah ◽  
Mallika Bhattacharyya ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Transcription Factor ◽  
Promoter Methylation ◽  
Messenger Rna ◽  
Dna Methyltransferase ◽  
Rna Expression ◽  
Betel Nut ◽  
Methylguanine Dna Methyltransferase ◽  
Related Transcription Factor ◽  
Transcription Factor 3

Promoter methylation reflects in the inactivation of different genes like O6-methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression. In addition, messenger RNA expression was correlated with different risk factors like tobacco, alcohol, betel nut consumption, and smoking habit. CpG methylation of O6-methylguanine-DNA methyltransferase promoter had a positive association in the development of esophageal cancer (p < 0.05), whereas runt-related transcription factor 3 promoter methylation showed no significant association (p = 1.0) to develop esophageal cancer. However, the non-CpG methylation, CHH, and CHG were significantly correlated with O6-methylguanine-DNA methyltransferase (p < 0.05) and runt-related transcription factor 3 (p < 0.05) promoters in the development of esophageal cancer. The number of cytosine converted to thymine (C→T) in O6-methylguanine-DNA methyltransferase promoter showed a significant correlation between cases and controls (p < 0.05), but in runt-related transcription factor 3 no such significant correlation was observed. Besides, messenger RNA expression was found to be significantly correlated with promoter hypermethylation of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in the context of CHG and CHH (p < 0.05). The CpG hypermethylation in O6-methylguanine-DNA methyltransferase showed positive (p < 0.05) association, whereas in runt-related transcription factor 3, it showed contrasting negative association (p = 0.23) with their messenger RNA expression. Tobacco, betel nut consumption, and smoking habits were associated with altered messenger RNA expression of O6-methylguanine-DNA methyltransferase (p < 0.05) and betel nut consumption and smoking habits were associated with runt-related transcription factor 3 (p < 0.05). There was no significant association between messenger RNA expression of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 with alcohol consumption (p = 0.32 and p = 0.15). In conclusion, our results suggest that an aberrant messenger RNA expression may be the outcome of CpG, CHG, and CHH methylation in O6-methylguanine-DNA methyltransferase, whereas outcome of CHG and CHH methylation in runt-related transcription factor 3 promoters along with risk factors such as consumption of tobacco, betel nut, and smoking habits in esophageal cancer from Northeast India.

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