Cargando…
Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis
Homogenous DNA methylation clearly affects clinical outcomes. However, less is known about the effects of heterogeneous methylation. We aimed to investigate the different effects between CASK promoter methylation heterogeneity and homogeneity on colorectal cancer (CRC) patients' prognosis. The...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655177/ https://www.ncbi.nlm.nih.gov/pubmed/33113509 http://dx.doi.org/10.18632/aging.103928 |
_version_ | 1783608187431157760 |
---|---|
author | Liu, Ying Huang, Hao Fu, Jinming Zhang, Yuanyuan Xu, Jing Zhang, Lei Sun, Simin Zhao, Liyuan Zhang, Ding Onwuka, Justina Ucheojor Sun, Hongru Cui, Binbin Zhao, Yashuang |
author_facet | Liu, Ying Huang, Hao Fu, Jinming Zhang, Yuanyuan Xu, Jing Zhang, Lei Sun, Simin Zhao, Liyuan Zhang, Ding Onwuka, Justina Ucheojor Sun, Hongru Cui, Binbin Zhao, Yashuang |
author_sort | Liu, Ying |
collection | PubMed |
description | Homogenous DNA methylation clearly affects clinical outcomes. However, less is known about the effects of heterogeneous methylation. We aimed to investigate the different effects between CASK promoter methylation heterogeneity and homogeneity on colorectal cancer (CRC) patients' prognosis. The methylation status of CASK in 296 tumor tissues and 255 adjacent normal tissues were evaluated using Methylation-sensitive high-resolution melting (MS-HRM). Digital MS-HRM (dMS-HRM) visualized heterogeneous methylation and subsequent sequencing provided exact patterns. Log-rank test and Cox regression model were adopted to assess the association between CASK methylation status and CRC prognosis with propensity score (PS) method to control confounding biases. Heterogeneous methylation was detected in both tumor (52.2%) and non-neoplastic tissue surrounding the tumor (62.4%). It occurred more frequently in lower levels of tumor invasion (P = 0.002) and male patients (P < 0.001). Compared with heterogeneous methylation, patients with CASK homogeneous methylation presented poorer overall survival (OS) (HR: 1.919, 95% CI: 1.146-3.212, P = 0.013) and disease-free survival (DFS) (HR: 1.913, 95% CI: 1.146-3.194, P = 0.013). This unfavorable effect still existed among older (≥ 50), Dukes staging C/D, and rectal cancer patients. MS-HRM and dMS-HRM when combined can assess the degree and complexity of heterogeneous methylation with a visible pattern. |
format | Online Article Text |
id | pubmed-7655177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-76551772020-11-19 Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis Liu, Ying Huang, Hao Fu, Jinming Zhang, Yuanyuan Xu, Jing Zhang, Lei Sun, Simin Zhao, Liyuan Zhang, Ding Onwuka, Justina Ucheojor Sun, Hongru Cui, Binbin Zhao, Yashuang Aging (Albany NY) Research Paper Homogenous DNA methylation clearly affects clinical outcomes. However, less is known about the effects of heterogeneous methylation. We aimed to investigate the different effects between CASK promoter methylation heterogeneity and homogeneity on colorectal cancer (CRC) patients' prognosis. The methylation status of CASK in 296 tumor tissues and 255 adjacent normal tissues were evaluated using Methylation-sensitive high-resolution melting (MS-HRM). Digital MS-HRM (dMS-HRM) visualized heterogeneous methylation and subsequent sequencing provided exact patterns. Log-rank test and Cox regression model were adopted to assess the association between CASK methylation status and CRC prognosis with propensity score (PS) method to control confounding biases. Heterogeneous methylation was detected in both tumor (52.2%) and non-neoplastic tissue surrounding the tumor (62.4%). It occurred more frequently in lower levels of tumor invasion (P = 0.002) and male patients (P < 0.001). Compared with heterogeneous methylation, patients with CASK homogeneous methylation presented poorer overall survival (OS) (HR: 1.919, 95% CI: 1.146-3.212, P = 0.013) and disease-free survival (DFS) (HR: 1.913, 95% CI: 1.146-3.194, P = 0.013). This unfavorable effect still existed among older (≥ 50), Dukes staging C/D, and rectal cancer patients. MS-HRM and dMS-HRM when combined can assess the degree and complexity of heterogeneous methylation with a visible pattern. Impact Journals 2020-10-28 /pmc/articles/PMC7655177/ /pubmed/33113509 http://dx.doi.org/10.18632/aging.103928 Text en Copyright: © 2020 Liu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Liu, Ying Huang, Hao Fu, Jinming Zhang, Yuanyuan Xu, Jing Zhang, Lei Sun, Simin Zhao, Liyuan Zhang, Ding Onwuka, Justina Ucheojor Sun, Hongru Cui, Binbin Zhao, Yashuang Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis |
title | Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis |
title_full | Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis |
title_fullStr | Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis |
title_full_unstemmed | Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis |
title_short | Colorectal cancer patients with CASK promotor heterogeneous and homogeneous methylation display different prognosis |
title_sort | colorectal cancer patients with cask promotor heterogeneous and homogeneous methylation display different prognosis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655177/ https://www.ncbi.nlm.nih.gov/pubmed/33113509 http://dx.doi.org/10.18632/aging.103928 |
work_keys_str_mv | AT liuying colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT huanghao colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT fujinming colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT zhangyuanyuan colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT xujing colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT zhanglei colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT sunsimin colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT zhaoliyuan colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT zhangding colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT onwukajustinaucheojor colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT sunhongru colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT cuibinbin colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis AT zhaoyashuang colorectalcancerpatientswithcaskpromotorheterogeneousandhomogeneousmethylationdisplaydifferentprognosis |