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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...

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Autores principales: 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
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
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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.
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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
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