Academic Journal
Open access-enabled evaluation of epigenetic age acceleration in colorectal cancer and development of a classifier with diagnostic potential.
| العنوان: | Open access-enabled evaluation of epigenetic age acceleration in colorectal cancer and development of a classifier with diagnostic potential. |
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| المؤلفون: | Widayati, TA, Schneider, J, Panteleeva, K, Chernysheva, E, Hrbkova, N, Beck, S, Voloshin, V, Chervova, O |
| سنة النشر: | 2023 |
| المجموعة: | Queen Mary University of London: Queen Mary Research Online (QMRO) |
| مصطلحات موضوعية: | CRC, colon tissue methylation, colorectal cancer, epigenetic age, epigenetic age acceleration, epigenetic clock |
| الوصف: | Aberrant DNA methylation (DNAm) is known to be associated with the aetiology of cancer, including colorectal cancer (CRC). In the past, the availability of open access data has been the main driver of innovative method development and research training. However, this is increasingly being eroded by the move to controlled access, particularly of medical data, including cancer DNAm data. To rejuvenate this valuable tradition, we leveraged DNAm data from 1,845 samples (535 CRC tumours, 522 normal colon tissues adjacent to tumours, 72 colorectal adenomas, and 716 normal colon tissues from healthy individuals) from 14 open access studies deposited in NCBI GEO and ArrayExpress. We calculated each sample's epigenetic age (EA) using eleven epigenetic clock models and derived the corresponding epigenetic age acceleration (EAA). For EA, we observed that most first- and second-generation epigenetic clocks reflect the chronological age in normal tissues adjacent to tumours and healthy individuals [e.g., Horvath (r = 0.77 and 0.79), Zhang elastic net (EN) (r = 0.70 and 0.73)] unlike the epigenetic mitotic clocks (EpiTOC, HypoClock, MiAge) (r < 0.3). For EAA, we used PhenoAge, Wu, and the above mitotic clocks and found them to have distinct distributions in different tissue types, particularly between normal colon tissues adjacent to tumours and cancerous tumours, as well as between normal colon tissues adjacent to tumours and normal colon tissue from healthy individuals. Finally, we harnessed these associations to develop a classifier using elastic net regression (with lasso and ridge regularisations) that predicts CRC diagnosis based on a patient's sex and EAAs calculated from histologically normal controls (i.e., normal colon tissues adjacent to tumours and normal colon tissue from healthy individuals). The classifier demonstrated good diagnostic potential with ROC-AUC = 0.886, which suggests that an EAA-based classifier trained on relevant data could become a tool to support diagnostic/prognostic decisions in CRC for ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1258648 - ? |
| اللغة: | English |
| تدمد: | 1664-8021 |
| Relation: | Front Genet; https://qmro.qmul.ac.uk/xmlui/handle/123456789/92544 |
| DOI: | 10.3389/fgene.2023.1258648 |
| الاتاحة: | https://qmro.qmul.ac.uk/xmlui/handle/123456789/92544 https://doi.org/10.3389/fgene.2023.1258648 |
| Rights: | Attribution 3.0 United States ; http://creativecommons.org/licenses/by/3.0/us/ |
| رقم الانضمام: | edsbas.7708E0A3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16648021 |
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| DOI: | 10.3389/fgene.2023.1258648 |