Comprehensive analysis of 5‐hydroxymethylcytosine in zw10 kinetochore protein as a promising biomarker for screening and diagnosis of early colorectal cancer
| Autor: | Guang Ji, Hanchen Xu, Yangxian Xu, Wenjun Zhou, Yanqi Dang, Li Zhang, Jingjuan Xu, Dan Hu, Chunlin Li, Yang Liu, Yingjue Tang, Zhenhua Yang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Colorectal cancer Cell Medicine (miscellaneous) colorectal cancer 5‐hydroxymethylcytosine 03 medical and health sciences 0302 clinical medicine medicine zw10 kinetochore protein Epigenetics Protein kinase B Research Articles PI3K/AKT/mTOR pathway lcsh:R5-920 Gene knockdown Cell growth business.industry medicine.disease digestive system diseases 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research biomarker Molecular Medicine Biomarker (medicine) lcsh:Medicine (General) business Research Article |
| Zdroj: | Clinical and Translational Medicine Clinical and Translational Medicine, Vol 10, Iss 3, Pp n/a-n/a (2020) |
| ISSN: | 2001-1326 |
| DOI: | 10.1002/ctm2.125 |
| Popis: | Background As a new epigenetic biomarker, 5‐hydroxymethylcytosine (5hmC) is broadly involved in various diseases including cancers. However, the function and diagnostic performance of 5hmC in colorectal cancer (CRC) remain unclear. Results High‐throughput sequencing was used to profile 5hmC levels in adjacent normal colon, advanced adenomas, and CRC. The expression and 5hmC levels in zw10 kinetochore protein (ZW10) were significantly increased in the tissues and blood samples for patients with advanced adenoma and CRC, and were much higher in the early stages of CRC (I and II). The receiver operating characteristic analysis had potential diagnostic value for CRC. The area under the curve (AUC) of ZW10 5hmC levels in tissue samples of CRC was 0.901. In blood samples, the AUC was 0.748 for CRC. In addition, the ZW10 5hmC level had much higher diagnostic performance in early stages of CRC (AUC = 0.857) than it did in advanced stages (AUC = 0.594). Compared with FHC cell, ZW10 expression in HT29 cell was significantly increased. The ZW10 knockdown could inhibit cell proliferation and the ZW10 overexpression could promote cell proliferation in HT‐29 cell. Furthermore, ZW10 knockdown inhibited AKT and mTOR phosphorylation, and ZW10 overexpression promoted AKT and mTOR phosphorylation. Conclusions The ZW10 5hmC level may serve as an effective epigenetic biomarker for minimally invasive screening and diagnosis of CRC, and it has higher diagnostic performance in early stages of CRC than it does in advanced stages. In addition, ZW10 could regulate CRC progression through the AKT‐mTOR signaling. |
| Databáze: | OpenAIRE |
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