scholarly journals Prognostic Value of microRNA-221/2 and 17-92 Families in Primary Glioblastoma Patients Treated with Postoperative Radiotherapy

2021 ◽  
Vol 22 (6) ◽  
pp. 2960
Author(s):  
Elena Schnabel ◽  
Maximilian Knoll ◽  
Christian Schwager ◽  
Rolf Warta ◽  
Andreas Mock ◽  
...  
Keyword(s):  
Survival Data ◽  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Postoperative Radiotherapy ◽  
The Cancer Genome Atlas ◽  
University Hospital ◽  
Primary Glioblastoma ◽  
Methylguanine Dna Methyltransferase ◽  
Independent Prognostic Marker ◽  
Taqman Technology

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients (n = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.

scholarly journals Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies

2021 ◽  
Vol 152 (3) ◽  
pp. 541-549
Author(s):  
Maher Kurdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa ◽  
Badrah Alghamdi ◽  
Yazid Maghrabi ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Chemotherapeutic Agents ◽  
Recurrence Interval ◽  
Mgmt Methylation ◽  
Conventional Radiotherapy ◽  
Methylguanine Dna Methyltransferase ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Temozolomide Chemotherapy

Abstract Objective To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. Method We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. Results No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. Conclusion Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

scholarly journals TCR Clonality and Genomic Instability Signatures as Prognostic Biomarkers in High Grade Serous Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4394
Author(s):  
Julie Lecuelle ◽  
Romain Boidot ◽  
Hugo Mananet ◽  
Valentin Derangère ◽  
Juliette Albuisson ◽  
...  
Keyword(s):  
T Cell ◽  
Genomic Instability ◽  
Survival Data ◽  
Prognostic Value ◽  
Prognostic Biomarker ◽  
Copy Number Variant ◽  
Cell Receptor ◽  
The Cancer Genome Atlas ◽  
High Grade ◽  
Cell Infiltrate

Purpose: Immune infiltration is a prognostic factor in high-grade serous ovarian carcinoma (HGSC) but immunotherapy efficacy is disappointing. Genomic instability is now used to guide the therapeutic value of PARP inhibitors. We aimed to investigate exome-derived parameters to assess the tumor microenvironment according to genomic instability profile. Methods: We used the HGSC TCGA (the cancer genome atlas) dataset with genomic characteristics, including homologous recombination deficiency (HRD), copy number variant (CNV) signatures, TCR (T cell receptor) clonality and abundance of tissue-infiltrating immune and stromal cell populations. We then investigated the relationship with survival data. Results: In 578 HGSC patients, HRD status, CNV signature 7 and TCR clonality were associated with longer survival. The combination of high CNV signature 7 expression and HRD status or high CNV signature 3 expression and high TCR clonality was associated with a trend towards longer survival compared to each variable alone. Combining T cell infiltrate and TCR clonality improved the prognostic value compared to T cells infiltration alone. Prognostic value of TCR clonality was confirmed in an independent cohort. Conclusions: TCR clonality is an emerging prognostic biomarker that improves T cell infiltrate information. Analysis of TCR clonality combined with genomic instability could be an interesting prognostic biomarker.

O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers

Lung Cancer ◽  
2010 ◽  
Vol 68 (3) ◽  
pp. 484-490 ◽  
Author(s):  
Pei-Fang Wu ◽  
Kuan-Ting Kuo ◽  
Lu-Ting Kuo ◽  
Yi-Ting Lin ◽  
Wei-Chung Lee ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Prognostic Value ◽  
Dna Methyltransferase ◽  
Lung Cancers ◽  
Methylguanine Dna Methyltransferase

scholarly journals Survival in patients with glioblastoma at a first progression does not correlate with isocitrate dehydrogenase (IDH)1 gene mutation status

2020 ◽  
Vol 51 (1) ◽  
pp. 45-53
Author(s):  
Yusuke Tabei ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Saki Shimizu ◽  
Kaori Suzuki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Methyltransferase ◽  
Median Overall Survival ◽  
Idh1 Mutation ◽  
Newly Diagnosed ◽  
Wild Type ◽  
Secondary Glioblastoma ◽  
Primary Glioblastoma ◽  
Methylguanine Dna Methyltransferase ◽  
Mutant Idh1

Abstract Backgrounds Mutations in the isocitrate dehydrogenase (IDH)1 gene are favourable prognostic factors in newly diagnosed diffuse gliomas, whereas it remains controversial in the recurrent glioblastoma setting. Methods A total of 171 patients with newly diagnosed glioblastoma, either ‘primary’ glioblastoma or ‘secondary’ glioblastoma, treated at Kyorin University Hospital or Japanese Red Cross Medical Center from 2000 to 2015 were included. Patients with confirmed IDH1 status and O6-methylguanine-DNA methyltransferase promoter methylation status were retrospectively analysed for overall survival from the initial diagnosis (n = 147) and after the first progression (n = 122). Results IDH1 mutation but not IDH2 was noted in 19 of 147 patients with glioblastoma (12.9%). In patients with ‘primary’ glioblastoma (n = 136), median overall survival after the first progression was 13.5 and 10.5 months for mutant IDH1 and wild-type IDH1 glioblastoma, respectively (P = 0.747). Multivariate analysis revealed O6-methylguanine-DNA methyltransferase promoter methylation, and Karnofsky Performance status 60 or higher, were independent prognostic factors for better overall survival after the first progression. When ‘primary’ glioblastoma and ‘secondary’ glioblastoma were combined, median overall survival from the first progression was not significantly different between the mutant IDH1 group (10.1 months) and wild-type IDH1 group (10.5 months) (P = 0.559), whereas median overall survival from the initial diagnosis was significantly different (47.5 months vs.18.3 months, respectively; P = 0.035). Conclusions These results suggest that IDH1 mutation may not be a prognostic factor for survival at the first progression of patients with ‘primary’ glioblastoma and pretreated ‘secondary’ glioblastoma, and further warrant investigation in prospective studies.

scholarly journals MRI-BASED DEEP LEARNING METHOD FOR DETERMINING METHYLATION STATUS OF THE O6-METHYLGUANINE–DNA METHYLTRANSFERASE PROMOTER OUTPERFORMS TISSUE BASED METHODS IN BRAIN GLIOMAS

2020 ◽  
Author(s):  
Chandan Ganesh Bangalore Yogananda ◽  
Bhavya R. Shah ◽  
Sahil S. Nalawade ◽  
Gowtham K. Murugesan ◽  
Frank F. Yu ◽  
...  
Keyword(s):  
Deep Learning ◽  
Dna Methyltransferase ◽  
Cross Validation ◽  
Brain Mri ◽  
Methylation Status ◽  
Magnetic Resonance Images ◽  
The Cancer Genome Atlas ◽  
Tumor Segmentation ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Promoter

ABSTRACTPURPOSEMethylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) promoter results in epigenetic silencing of the MGMT enzyme and confers an improved prognosis and treatment response in gliomas. The purpose of this study was to develop a deep-learning network for determining the methylation status of the MGMT Promoter in gliomas using T2-w magnetic resonance images only.METHODSBrain MRI and corresponding genomic information were obtained for 247 subjects from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). 163 subjects had a methylated MGMT promoter. A T2-w image only network (MGMT-net) was developed to determine MGMT promoter methylation status and simultaneous single label tumor segmentation. The network was trained using 3D-Dense-UNets. Three-fold cross-validation was performed to generalize the networks’ performance. Dice-scores were computed to determine tumor segmentation accuracy.RESULTSMGMT-net demonstrated a mean cross validation accuracy of 94.73% across the 3 folds (95.12%, 93.98%, and 95.12%, standard dev=0.66) in predicting MGMT methylation status with a sensitivity and specificity of 96.31% ±0.04 and 91.66% ±2.06, respectively and a mean AUC of 0.93 ±0.01. The whole tumor segmentation mean Dice-score was 0.82 ± 0.008.CONCLUSIONWe demonstrate high classification accuracy in predicting the methylation status of the MGMT promoter using only T2-w MR images that surpasses the sensitivity, specificity, and accuracy of invasive histological methods such as pyrosequencing, methylation-specific PCR, and immunofluorescence methods. This represents an important milestone toward using MRI to predict glioma histology, prognosis, and response to treatment.

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