Cargando…
Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma
Clear-cell renal cell carcinoma (ccRCC) is a common aggressive urinary malignant tumor that cannot be easily diagnosed at an early stage. The DNA methylation occurs within promoter before precancerous lesion plays a pivotal role that could help us in diagnosing and understanding ccRCC. In this study...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660223/ https://www.ncbi.nlm.nih.gov/pubmed/29079774 http://dx.doi.org/10.1038/s41598-017-14314-y |
_version_ | 1783274258661638144 |
---|---|
author | Gu, Yinmin Zou, Yi Ming Lei, Danqing Huang, Yuanjie Li, Weidong Mo, Zengnan Hu, Yanling |
author_facet | Gu, Yinmin Zou, Yi Ming Lei, Danqing Huang, Yuanjie Li, Weidong Mo, Zengnan Hu, Yanling |
author_sort | Gu, Yinmin |
collection | PubMed |
description | Clear-cell renal cell carcinoma (ccRCC) is a common aggressive urinary malignant tumor that cannot be easily diagnosed at an early stage. The DNA methylation occurs within promoter before precancerous lesion plays a pivotal role that could help us in diagnosing and understanding ccRCC. In this study, based on a whole-genome promoter DNA methylation profiling, we used shrunken centroids classifier method to identify a CpG-based biomarker that is capable of differentiating between ccRCC tumor and adjacent tissues. The biomarker was validated in 19 ccRCCs and three public datasets. We found that both CYP4B1 and RAB25 are downregulated with promoter hypermethylation and CA9 is upregulated with promoter hypomethylation, and we validated their mRNA differential expressions in 19 ccRCCs and 10 GEO datasets. We further confirmed that hypermethylated RAB25 is inversely correlated with its mRNA level. Log-rank test showed that ccRCC patients with low levels of CA9 promoter methylation had a higher survival rate. This reveals clinically a potential biomarker for use in early detection for ccRCC, and provides a better understanding of carcinogenesis. |
format | Online Article Text |
id | pubmed-5660223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56602232017-11-01 Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma Gu, Yinmin Zou, Yi Ming Lei, Danqing Huang, Yuanjie Li, Weidong Mo, Zengnan Hu, Yanling Sci Rep Article Clear-cell renal cell carcinoma (ccRCC) is a common aggressive urinary malignant tumor that cannot be easily diagnosed at an early stage. The DNA methylation occurs within promoter before precancerous lesion plays a pivotal role that could help us in diagnosing and understanding ccRCC. In this study, based on a whole-genome promoter DNA methylation profiling, we used shrunken centroids classifier method to identify a CpG-based biomarker that is capable of differentiating between ccRCC tumor and adjacent tissues. The biomarker was validated in 19 ccRCCs and three public datasets. We found that both CYP4B1 and RAB25 are downregulated with promoter hypermethylation and CA9 is upregulated with promoter hypomethylation, and we validated their mRNA differential expressions in 19 ccRCCs and 10 GEO datasets. We further confirmed that hypermethylated RAB25 is inversely correlated with its mRNA level. Log-rank test showed that ccRCC patients with low levels of CA9 promoter methylation had a higher survival rate. This reveals clinically a potential biomarker for use in early detection for ccRCC, and provides a better understanding of carcinogenesis. Nature Publishing Group UK 2017-10-27 /pmc/articles/PMC5660223/ /pubmed/29079774 http://dx.doi.org/10.1038/s41598-017-14314-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Gu, Yinmin Zou, Yi Ming Lei, Danqing Huang, Yuanjie Li, Weidong Mo, Zengnan Hu, Yanling Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma |
title | Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma |
title_full | Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma |
title_fullStr | Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma |
title_full_unstemmed | Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma |
title_short | Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma |
title_sort | promoter dna methylation analysis reveals a novel diagnostic cpg-based biomarker and rab25 hypermethylation in clear cell renel cell carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660223/ https://www.ncbi.nlm.nih.gov/pubmed/29079774 http://dx.doi.org/10.1038/s41598-017-14314-y |
work_keys_str_mv | AT guyinmin promoterdnamethylationanalysisrevealsanoveldiagnosticcpgbasedbiomarkerandrab25hypermethylationinclearcellrenelcellcarcinoma AT zouyiming promoterdnamethylationanalysisrevealsanoveldiagnosticcpgbasedbiomarkerandrab25hypermethylationinclearcellrenelcellcarcinoma AT leidanqing promoterdnamethylationanalysisrevealsanoveldiagnosticcpgbasedbiomarkerandrab25hypermethylationinclearcellrenelcellcarcinoma AT huangyuanjie promoterdnamethylationanalysisrevealsanoveldiagnosticcpgbasedbiomarkerandrab25hypermethylationinclearcellrenelcellcarcinoma AT liweidong promoterdnamethylationanalysisrevealsanoveldiagnosticcpgbasedbiomarkerandrab25hypermethylationinclearcellrenelcellcarcinoma AT mozengnan promoterdnamethylationanalysisrevealsanoveldiagnosticcpgbasedbiomarkerandrab25hypermethylationinclearcellrenelcellcarcinoma AT huyanling promoterdnamethylationanalysisrevealsanoveldiagnosticcpgbasedbiomarkerandrab25hypermethylationinclearcellrenelcellcarcinoma |