Discovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer
| العنوان: | Discovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer |
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| المؤلفون: | Gerda Egger, Andrea Haitel, Dafina Ilijazi, Luca Molinaro, Benjamin Pradere, Andreas Bruchbacher, Ursula Lemberger, Martin Susani, Francesco Soria, Shahrokh F. Shariat, Shoji Kimura, Walter Pulverer, Stephan Pabinger, Melanie R. Hassler, Mohammad Abufaraj, Andreas Weinhäusel, David D'Andrea, Evi Comploj, Anna Graf, Iris E Ertl, Armin Pycha |
| المصدر: | Cells Volume 9 Issue 8 Cells, Vol 9, Iss 1839, p 1839 (2020) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_treatment, Bacillus Calmette-Guérin, BCG refractory, bladder cancer, DNA methylation marker, high-risk bladder cancer, Illumina MethylationEPIC BeadChip, urothelial cancer, Adjuvants, Immunologic, Aged, Aged, 80 and over, BCG Vaccine, Biomarkers, Tumor, CpG Islands, Female, Genome-Wide Association Study, Heterochromatin, Humans, Immunotherapy, Middle Aged, Promoter Regions, Genetic, Treatment Outcome, Urinary Bladder Neoplasms, DNA Methylation, chemistry.chemical_compound, 0302 clinical medicine, Immunologic, 80 and over, lcsh:QH301-705.5, Tumor, General Medicine, Methylation, CpG site, 030220 oncology & carcinogenesis, DNA methylation, Biology, Article, Promoter Regions, 03 medical and health sciences, Genetic, medicine, Adjuvants, Gene, Bladder cancer, fungi, Promoter, medicine.disease, 030104 developmental biology, lcsh:Biology (General), chemistry, Cancer research, bacteria, Biomarkers, DNA |
| الوصف: | Background: Bacillus Calmette-Gué rin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting. Methods: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy. Genome-wide DNA methylation profiles of DNA isolated from tumors of 26 BCG responders and 27 failures were obtained using the Infinium MethylationEPIC BeadChip. Results: Distinct DNA methylation patterns were found by genome-wide analysis in the two groups. Differentially methylated CpG sites were predominantly located in gene promoters and gene bodies associated with bacterial invasion of epithelial cells, chemokine signaling, endocytosis, and focal adhesion. In total, 40 genomic regions with a significant difference in methylation between responders and failures were detected. The differential methylation state of six of these regions, localized in the promoters of the genes GPR158, KLF8, C12orf42, WDR44, FLT1, and CHST11, were internally validated by bisulfite-sequencing. GPR158 promoter hypermethylation was the best predictor of BCG failure with an AUC of 0.809 (p-value < 0.001). Conclusions: Tumors from BCG responders and BCG failures harbor distinct DNA methylation profiles. Differentially methylated DNA regions were detected in genes related to pathways involved in bacterial invasion of cells or focal adhesion. We identified candidate DNA methylation biomarkers that may help to predict patient prognosis after external validation in larger, well-designed cohorts. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| DOI: | 10.3390/cells9081839 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08b7e4dc277c7315a68dc085ffe43cea |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....08b7e4dc277c7315a68dc085ffe43cea |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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| DOI: | 10.3390/cells9081839 |