A Novel Pseudogene Methylation Signature to Predict Temozolomide Outcome in Non-G-CIMP Glioblastomas
| العنوان: | A Novel Pseudogene Methylation Signature to Predict Temozolomide Outcome in Non-G-CIMP Glioblastomas |
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| المؤلفون: | Bowen Li, Jiu Wang, Fangfang Liu, Rui Li, Weihong Hu, Amandine Etcheverry, Marc Aubry, Jean Mosser, Anan Yin, Xiang Zhang, Yuanming Wu, Kun Chen, Yalong He, Li Wang |
| المساهمون: | Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), National Natural Science Foundation of China [81402049, 81802486, 81671476, 31570906], Shandong Province Natural Science Foundation [ZR2020QH0233], Key Research and Development Plan in Shaanxi [2019SF-059, 2020SF-204], Key Innovative Project in Shaanxi [2021ZDLSF02-02], Brittany Region, FEDER (Europe) |
| المصدر: | Journal of Oncology Journal of Oncology, 2022, 2022, pp.6345160. ⟨10.1155/2022/6345160⟩ |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Oncology, Article Subject, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.CAN]Life Sciences [q-bio]/Cancer, neoplasms |
| الوصف: | International audience; Objective. Alterations in the methylation state of pseudogenes may serve as clinically useful biomarkers of glioblastomas (GBMs) that do not have glioma-CpG island methylator phenotype (G-CIMP).Methods. Non-G-CIMP GBM datasets were included for evaluation, and a RISK-score signature was determined from the methylation state of pseudogene loci. Both bioinformatic and experimental analyses were performed for biological validation.Results. By integrating clinical information with DNA methylation microarray data, we screened a panel of eight CpGs from discovery cohorts of non-G-CIMP GBMs. Each CpG could accurately and independently predict the prognosis of patients under a treatment regime that combined radiotherapy (RT) and temozolomide (TMZ). The 8-CpG signature appeared to show opposite prognostic correlations between patients treated with RT/TMZ and those treated with RT monotherapy. The analyses further indicated that this signature had predictive value for TMZ efficacy because different survival benefits between RT/TMZ and RT therapies were observed in each risk subgroup. The incorporation of other risk factors, such as age and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, with our pseudogene methylation signature could provide precise risk classification. In vitro experimental data revealed that two locus-specific pseudogenes (ZNF767P and CLEC4GP1) may modulate TMZ resistance via distinct mechanisms in GBM cells.Conclusion. The biologically and clinically relevant RISK-score signature, based on pseudogene methylation loci, may offer information for predicting TMZ responses of non-G-CIMP GBMs, that is independent from, but complementary to, MGMT-based approaches. |
| وصف الملف: | text/xhtml |
| تدمد: | 1687-8450 1687-8469 |
| DOI: | 10.1155/2022/6345160⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::64766f7b8d27ef44519a439f5b4011e5 https://pubmed.ncbi.nlm.nih.gov/35712126 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....64766f7b8d27ef44519a439f5b4011e5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16878450 16878469 |
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| DOI: | 10.1155/2022/6345160⟩ |