A three-gene DNA methylation biomarker accurately classifies early stage prostate cancer
| العنوان: | A three-gene DNA methylation biomarker accurately classifies early stage prostate cancer |
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| المؤلفون: | Laura A. Lee, Tanya Sack, Robert J. Gooding, Rachel Dunn, Joseph L. Chin, Atsunari Kawashima, Audrey Ellis, Karl-Philippe Guérard, Elizabeth Marra, Glenn Bauman, Vinolia Arthur-Hayward, Chelsea L. Jackson, Fadi Brimo, Simone Chevalier, Khurram M. Siddiqui, David M. Berman, Karen Mackie, Thomas Wessel, Dan Dion, Tamara Jamaspishvili, Suzanne Boursalie, Anna Ying-Wah Lee, Lee-Anne Pickard, Jacques Lapointe, Palak G. Patel, Eleonora Scarlata, Nathan E How, John M. S. Bartlett, John B. A. Okello, Khalil Hetou, Madeleine Moussa, Paul C. Boutros |
| المصدر: | Medical Biophysics Publications Patel, P G, Wessel, T, Kawashima, A, Okello, J B, Jamaspishvili, T, Guerard, K-P, Lee, L, Ying-Wah Lee, A, E. How, N, Dion, D, Scarlata, E, L. Jackson, C, Boursalie, S, Sack, T, Dunn, R, Moussa, M, Mackie, K, Ellis, A, Marra, E, Chin, J, Siddiqui, K, Hetou, K, Pickard, L-A, Arthur Hayward, V, Bauman, G, Chevalier, S, Brimo, F, Boutros, P, Lapointe, J, Bartlett, J, J. Gooding, R & M. Berman, D 2019, ' A three gene DNA methylation biomarker accurately classifies early stage prostate cancer ', Prostate . https://doi.org/10.1002/pros.23895 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, medicine.medical_specialty, Urology, medicine.medical_treatment, prostate cancer diagnosis, Biology, Sensitivity and Specificity, Epigenesis, Genetic, 03 medical and health sciences, GSTP1, Prostate cancer, 0302 clinical medicine, Prostate, Internal medicine, medicine, Biomarkers, Tumor, Humans, Cancer epigenetics, Extracellular Matrix Proteins, DNA methylation, biomarker discovery and validation, Prostatectomy, Cancer, Prostatic Neoplasms, Reproducibility of Results, DNA, DNA Methylation, medicine.disease, cancer epigenetics, 030104 developmental biology, medicine.anatomical_structure, Glutathione S-Transferase pi, 030220 oncology & carcinogenesis, Biomarker (medicine), Intercellular Signaling Peptides and Proteins, Proteoglycans |
| الوصف: | Background We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations. Materials and methods We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real-time methylation-specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated. Results In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S-transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest-specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation. Conclusion We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three-gene biomarker represents a promising basis for more accurate prostate cancer diagnosis. |
| وصف الملف: | application/pdf |
| تدمد: | 1097-0045 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91ff13d6577bd2a95ff43c8114d9bb6f https://pubmed.ncbi.nlm.nih.gov/31433512 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....91ff13d6577bd2a95ff43c8114d9bb6f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970045 |
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