Impact of line-1 hypomethylation on the clinicopathological and molecular features of colorectal cancer patients

Tai Chuan Kuan; Pei Ching Lin; Shung Haur Yang; Chun Chi Lin; Yuan Tzu Lan; Hung Hsin Lin; Wen Yi Liang; Wei Shone Chen; Jen Kou Lin; Jeng Kai Jiang; Shih Ching Chang

doi:10.1371/journal.pone.0197681

Impact of line-1 hypomethylation on the clinicopathological and molecular features of colorectal cancer patients

Tai Chuan Kuan, Pei Ching Lin, Shung Haur Yang, Chun Chi Lin, Yuan Tzu Lan, Hung Hsin Lin, Wen Yi Liang, Wei Shone Chen, Jen Kou Lin, Jeng Kai Jiang^*, Shih Ching Chang

^*Corresponding author for this work

Department of Surgery

Research output: Contribution to journal › Article › peer-review

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Abstract

Recent studies suggest that aberrant DNA methylation might occur early and commonly in colorectal tumorigenesis. In 111 normal subjects, the mean LINE-1 methylation level of peripheral blood was 81.0 ± 5.7%. Of 143 colorectal cancer (CRC) patients, the mean level of LINE-1 methylation was 60.5 ± 12.5%. We defined below 60% as cut-off value of LINE-1 hypomethylation, and 93 cases (65.0%) had LINE-1 hypomethylation in the tumor tissue. LINE-1 hypomethylation was not associated with any other clinical features. There was a trend that LINE-1 hypomethylation tumors were associated with advanced disease, but it did not reach statistical significance. There was no significant association between mutations of 12 genes, MSI-high, EMAST, and LINE-1 hypomethylation level. The median follow-up was 61.2 months. Five-year disease-free survival (DFS) and overall survival curves of patients with LINE-1 hypomethylation tumors were significantly lower than those of patients with normal LINE-1 methylation tumors (p = 0.032 and 0.001, respectively). Multivariate analysis showed that only TNM staging was an independent prognostic factor for CRC patients including DFS and overall survival (OS). LINE-1 did not impact patients’ outcomes in multivariate analysis including DFS and OS. In conclusion, LINE-1 hypomethylation is marginally related to advanced stage CRC and impacts patients’ outcomes in univariate analysis.

Original language	English
Article number	e0197681
Journal	PLoS ONE
Volume	13
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0197681
State	Published - May 2018

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title = "Impact of line-1 hypomethylation on the clinicopathological and molecular features of colorectal cancer patients",

abstract = "Recent studies suggest that aberrant DNA methylation might occur early and commonly in colorectal tumorigenesis. In 111 normal subjects, the mean LINE-1 methylation level of peripheral blood was 81.0 ± 5.7%. Of 143 colorectal cancer (CRC) patients, the mean level of LINE-1 methylation was 60.5 ± 12.5%. We defined below 60% as cut-off value of LINE-1 hypomethylation, and 93 cases (65.0%) had LINE-1 hypomethylation in the tumor tissue. LINE-1 hypomethylation was not associated with any other clinical features. There was a trend that LINE-1 hypomethylation tumors were associated with advanced disease, but it did not reach statistical significance. There was no significant association between mutations of 12 genes, MSI-high, EMAST, and LINE-1 hypomethylation level. The median follow-up was 61.2 months. Five-year disease-free survival (DFS) and overall survival curves of patients with LINE-1 hypomethylation tumors were significantly lower than those of patients with normal LINE-1 methylation tumors (p = 0.032 and 0.001, respectively). Multivariate analysis showed that only TNM staging was an independent prognostic factor for CRC patients including DFS and overall survival (OS). LINE-1 did not impact patients{\textquoteright} outcomes in multivariate analysis including DFS and OS. In conclusion, LINE-1 hypomethylation is marginally related to advanced stage CRC and impacts patients{\textquoteright} outcomes in univariate analysis.",

author = "Kuan, {Tai Chuan} and Lin, {Pei Ching} and Yang, {Shung Haur} and Lin, {Chun Chi} and Lan, {Yuan Tzu} and Lin, {Hung Hsin} and Liang, {Wen Yi} and Chen, {Wei Shone} and Lin, {Jen Kou} and Jiang, {Jeng Kai} and Chang, {Shih Ching}",

note = "Publisher Copyright: {\textcopyright} 2018 Kuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2018",

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AU - Kuan, Tai Chuan

AU - Lin, Pei Ching

AU - Yang, Shung Haur

AU - Lin, Chun Chi

AU - Lan, Yuan Tzu

AU - Lin, Hung Hsin

AU - Liang, Wen Yi

AU - Chen, Wei Shone

AU - Lin, Jen Kou

AU - Jiang, Jeng Kai

AU - Chang, Shih Ching

N1 - Publisher Copyright: © 2018 Kuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2018/5

Y1 - 2018/5

N2 - Recent studies suggest that aberrant DNA methylation might occur early and commonly in colorectal tumorigenesis. In 111 normal subjects, the mean LINE-1 methylation level of peripheral blood was 81.0 ± 5.7%. Of 143 colorectal cancer (CRC) patients, the mean level of LINE-1 methylation was 60.5 ± 12.5%. We defined below 60% as cut-off value of LINE-1 hypomethylation, and 93 cases (65.0%) had LINE-1 hypomethylation in the tumor tissue. LINE-1 hypomethylation was not associated with any other clinical features. There was a trend that LINE-1 hypomethylation tumors were associated with advanced disease, but it did not reach statistical significance. There was no significant association between mutations of 12 genes, MSI-high, EMAST, and LINE-1 hypomethylation level. The median follow-up was 61.2 months. Five-year disease-free survival (DFS) and overall survival curves of patients with LINE-1 hypomethylation tumors were significantly lower than those of patients with normal LINE-1 methylation tumors (p = 0.032 and 0.001, respectively). Multivariate analysis showed that only TNM staging was an independent prognostic factor for CRC patients including DFS and overall survival (OS). LINE-1 did not impact patients’ outcomes in multivariate analysis including DFS and OS. In conclusion, LINE-1 hypomethylation is marginally related to advanced stage CRC and impacts patients’ outcomes in univariate analysis.

AB - Recent studies suggest that aberrant DNA methylation might occur early and commonly in colorectal tumorigenesis. In 111 normal subjects, the mean LINE-1 methylation level of peripheral blood was 81.0 ± 5.7%. Of 143 colorectal cancer (CRC) patients, the mean level of LINE-1 methylation was 60.5 ± 12.5%. We defined below 60% as cut-off value of LINE-1 hypomethylation, and 93 cases (65.0%) had LINE-1 hypomethylation in the tumor tissue. LINE-1 hypomethylation was not associated with any other clinical features. There was a trend that LINE-1 hypomethylation tumors were associated with advanced disease, but it did not reach statistical significance. There was no significant association between mutations of 12 genes, MSI-high, EMAST, and LINE-1 hypomethylation level. The median follow-up was 61.2 months. Five-year disease-free survival (DFS) and overall survival curves of patients with LINE-1 hypomethylation tumors were significantly lower than those of patients with normal LINE-1 methylation tumors (p = 0.032 and 0.001, respectively). Multivariate analysis showed that only TNM staging was an independent prognostic factor for CRC patients including DFS and overall survival (OS). LINE-1 did not impact patients’ outcomes in multivariate analysis including DFS and OS. In conclusion, LINE-1 hypomethylation is marginally related to advanced stage CRC and impacts patients’ outcomes in univariate analysis.

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Impact of line-1 hypomethylation on the clinicopathological and molecular features of colorectal cancer patients

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