دورية أكاديمية
Integrative analysis identifies an immune-relevant epigenetic signature for prognostication of non-G-CIMP glioblastomas
| العنوان: | Integrative analysis identifies an immune-relevant epigenetic signature for prognostication of non-G-CIMP glioblastomas |
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| المؤلفون: | Anan Yin, Zhende Shang, Amandine Etcheverry, Yalong He, Marc Aubry, Nan Lu, Yuhe Liu, Jean Mosser, Wei Lin, Xiang Zhang, Yu Dong |
| المصدر: | OncoImmunology, Vol 10, Iss 1 (2021) |
| بيانات النشر: | Taylor & Francis Group, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | glioblastomas, glioma-cpgs island methylator phenotype, dna methylation, prognostic biomarker, immune phenotype, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | The clinical and molecular implications of DNA methylation alterations remain unclear among the majority of glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP); integrative multi-level molecular profiling may provide useful information. Independent cohorts of non-G-CIMP GBMs or IDH wild type (wt) lower-grade gliomas (LGGs) from local and public databases with DNA methylation and gene expression microarray data were included for discovery and validation of a multimarker signature, combined using a RISK score model. Bioinformatic and in vitro functional analyses were employed for biological validation. Using a strict multistep selection approach, we identified eight CpGs, each of which was significantly correlated with overall survival (OS) of non-G-CIMP GBMs, independent of age, the O-6-methylguanine-DNA methyltransferase (MGMT) methylation status, treatments and other identified CpGs. An epigenetic RISK signature of the 8 CpGs was developed and validated to robustly and independently prognosticate prognosis in different cohorts of not only non-G-GIMP GBMs, but also IDHwt LGGs. It also showed good discriminating value in stratified cohorts by current clinical and molecular factors. Bioinformatic analysis revealed consistent correlation of the epigenetic signature to distinct immune-relevant transcriptional profiles of GBM bulks. Functional experiments showed that S100A2 appeared to be epigenetically regulated by one identified CpG and was associated with GBM cell proliferation, apoptosis, invasion, migration and immunosuppression. The prognostic 8-CpGs RISK score signature may be of promising value for refining current glioma risk classification, and its potential links to distinct immune phenotypes make it a promising biomarker candidate for predicting response to anti-glioma immunotherapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162-402X 2162402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2021.1902071 |
| URL الوصول: | https://doaj.org/article/8800ac7fe4a64794b02ac89cba1fa96a |
| رقم الأكسشن: | edsdoj.8800ac7fe4a64794b02ac89cba1fa96a |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2021.1902071 |