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DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study

Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colore...

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Autores principales: Kuan, Jen Chun, Wu, Chang Chieh, Sun, Chien An, Chu, Chi Ming, Lin, Fu Gong, Hsu, Chih Hsiung, Kan, Po-Chieh, Lin, Shih-Chieh, Yang, Tsan, Chou, Yu-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376718/
https://www.ncbi.nlm.nih.gov/pubmed/25815725
http://dx.doi.org/10.1371/journal.pone.0123396
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author Kuan, Jen Chun
Wu, Chang Chieh
Sun, Chien An
Chu, Chi Ming
Lin, Fu Gong
Hsu, Chih Hsiung
Kan, Po-Chieh
Lin, Shih-Chieh
Yang, Tsan
Chou, Yu-Ching
author_facet Kuan, Jen Chun
Wu, Chang Chieh
Sun, Chien An
Chu, Chi Ming
Lin, Fu Gong
Hsu, Chih Hsiung
Kan, Po-Chieh
Lin, Shih-Chieh
Yang, Tsan
Chou, Yu-Ching
author_sort Kuan, Jen Chun
collection PubMed
description Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colorectal cancer (CRC). A cohort study of 215 patients with CRC (mean age 64.32 years; 50.5% of men) from Tri-Service General Hospital in Taiwan examined the association between cancer stage and risk of CRC recurrence and mortality. A Cox proportional hazard model was used to analyze patient methylation status and clinical information at study entry, and their associations with CRC recurrence and mortality during follow-up. The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in tumor tissues, with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 9.64 (2.92–31.81), 8.29 (3.40–20.22), and 11.83 (3.49–40.12), respectively. When analyzing normal tissues, we observed similar risk of CRC recurrence with adjusted HRs (95% CI) of 10.85 (4.06–28.96), 9.04 (3.79–21.54), and 12.61 (4.90–32.44), respectively. For combined analyses, the risk of recurrence in the patients in advanced stage with DNA methylation in both normal and tumor tissues, compared with local stage with unmethylation, was increased with adjusted HR (95% CI) of 9.37 (3.36–26.09). In the advanced stage patients, methylation status and tissue subtype were associated with increased risk of 5-year cumulative CRC recurrence (p < 0.001). This study demonstrates that clustering DNA methylation status according to cancer stage and tissue subtype is critical for the assessment of risk of recurrence in CRC patients and also indicated an underlying mechanism.
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spelling pubmed-43767182015-04-04 DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study Kuan, Jen Chun Wu, Chang Chieh Sun, Chien An Chu, Chi Ming Lin, Fu Gong Hsu, Chih Hsiung Kan, Po-Chieh Lin, Shih-Chieh Yang, Tsan Chou, Yu-Ching PLoS One Research Article Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colorectal cancer (CRC). A cohort study of 215 patients with CRC (mean age 64.32 years; 50.5% of men) from Tri-Service General Hospital in Taiwan examined the association between cancer stage and risk of CRC recurrence and mortality. A Cox proportional hazard model was used to analyze patient methylation status and clinical information at study entry, and their associations with CRC recurrence and mortality during follow-up. The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in tumor tissues, with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 9.64 (2.92–31.81), 8.29 (3.40–20.22), and 11.83 (3.49–40.12), respectively. When analyzing normal tissues, we observed similar risk of CRC recurrence with adjusted HRs (95% CI) of 10.85 (4.06–28.96), 9.04 (3.79–21.54), and 12.61 (4.90–32.44), respectively. For combined analyses, the risk of recurrence in the patients in advanced stage with DNA methylation in both normal and tumor tissues, compared with local stage with unmethylation, was increased with adjusted HR (95% CI) of 9.37 (3.36–26.09). In the advanced stage patients, methylation status and tissue subtype were associated with increased risk of 5-year cumulative CRC recurrence (p < 0.001). This study demonstrates that clustering DNA methylation status according to cancer stage and tissue subtype is critical for the assessment of risk of recurrence in CRC patients and also indicated an underlying mechanism. Public Library of Science 2015-03-27 /pmc/articles/PMC4376718/ /pubmed/25815725 http://dx.doi.org/10.1371/journal.pone.0123396 Text en © 2015 Kuan et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Kuan, Jen Chun
Wu, Chang Chieh
Sun, Chien An
Chu, Chi Ming
Lin, Fu Gong
Hsu, Chih Hsiung
Kan, Po-Chieh
Lin, Shih-Chieh
Yang, Tsan
Chou, Yu-Ching
DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study
title DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study
title_full DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study
title_fullStr DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study
title_full_unstemmed DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study
title_short DNA Methylation Combinations in Adjacent Normal Colon Tissue Predict Cancer Recurrence: Evidence from a Clinical Cohort Study
title_sort dna methylation combinations in adjacent normal colon tissue predict cancer recurrence: evidence from a clinical cohort study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376718/
https://www.ncbi.nlm.nih.gov/pubmed/25815725
http://dx.doi.org/10.1371/journal.pone.0123396
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