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Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX

BACKGROUND: Profound methylation of CpG islands constitutes a distinct molecular subtype of colorectal cancer (CRC). The frequencies of methylation in CRC vary according to clinico-pathological characteristics including sex. However, interaction between these characteristics and prognostic influence...

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Autores principales: Lee, Dae-Won, Han, Sae-Won, Cha, Yongjun, Rhee, Ye Young, Bae, Jeong Mo, Cho, Nam-Yun, Lee, Kyung-Hun, Kim, Tae-Yong, Oh, Do-Youn, Im, Seock-Ah, Bang, Yung-Jue, Jeong, Seung-Yong, Park, Kyu Joo, Kang, Gyeong Hoon, Kim, Tae-You
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495938/
https://www.ncbi.nlm.nih.gov/pubmed/26157509
http://dx.doi.org/10.1186/s13148-015-0106-0
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author Lee, Dae-Won
Han, Sae-Won
Cha, Yongjun
Rhee, Ye Young
Bae, Jeong Mo
Cho, Nam-Yun
Lee, Kyung-Hun
Kim, Tae-Yong
Oh, Do-Youn
Im, Seock-Ah
Bang, Yung-Jue
Jeong, Seung-Yong
Park, Kyu Joo
Kang, Gyeong Hoon
Kim, Tae-You
author_facet Lee, Dae-Won
Han, Sae-Won
Cha, Yongjun
Rhee, Ye Young
Bae, Jeong Mo
Cho, Nam-Yun
Lee, Kyung-Hun
Kim, Tae-Yong
Oh, Do-Youn
Im, Seock-Ah
Bang, Yung-Jue
Jeong, Seung-Yong
Park, Kyu Joo
Kang, Gyeong Hoon
Kim, Tae-You
author_sort Lee, Dae-Won
collection PubMed
description BACKGROUND: Profound methylation of CpG islands constitutes a distinct molecular subtype of colorectal cancer (CRC). The frequencies of methylation in CRC vary according to clinico-pathological characteristics including sex. However, interaction between these characteristics and prognostic influence of methylation status has not been clearly defined. We have investigated the prognostic role of promoter methylation using eight CpG island methylator phenotype (CIMP) markers in 497 stage II or III CRC patients who underwent curative resection followed by adjuvant FOLFOX. Overall survival (OS) and disease-free survival (DFS) were compared between subgroups classified by methylation status, and interactions with clinico-pathological features were analyzed. RESULTS: CIMP-high (≥5 methylated loci) and concurrent methylation in NEUROG1 and CDKN2A (p16) were found in 5.8 and 7.9 % of patients, respectively. Although CIMP-high status was not associated with survival, concurrent methylation in NEUROG1 and CDKN2A (p16) was associated with shorter OS and DFS. Moreover, the prognostic role of the concurrent methylation was different among sex. The negative prognostic impact was only observed in male but not in female (interaction p value = 0.026 for OS and 0.011 for DFS). In male, the 5-year OS was 61.6 % in concurrent methylation (+) and 91.7 % in concurrent methylation (−) (p < 0.001) whereas it was 95.0 and 92.8 % in female, respectively (p = 0.78). CONCLUSIONS: Concurrent methylation in NEUROG1 and CDKN2A is associated with poor survival in CRC treated with adjuvant FOLFOX. Interaction analysis indicates that the prognostic role is different according to sex.
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spelling pubmed-44959382015-07-09 Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX Lee, Dae-Won Han, Sae-Won Cha, Yongjun Rhee, Ye Young Bae, Jeong Mo Cho, Nam-Yun Lee, Kyung-Hun Kim, Tae-Yong Oh, Do-Youn Im, Seock-Ah Bang, Yung-Jue Jeong, Seung-Yong Park, Kyu Joo Kang, Gyeong Hoon Kim, Tae-You Clin Epigenetics Research BACKGROUND: Profound methylation of CpG islands constitutes a distinct molecular subtype of colorectal cancer (CRC). The frequencies of methylation in CRC vary according to clinico-pathological characteristics including sex. However, interaction between these characteristics and prognostic influence of methylation status has not been clearly defined. We have investigated the prognostic role of promoter methylation using eight CpG island methylator phenotype (CIMP) markers in 497 stage II or III CRC patients who underwent curative resection followed by adjuvant FOLFOX. Overall survival (OS) and disease-free survival (DFS) were compared between subgroups classified by methylation status, and interactions with clinico-pathological features were analyzed. RESULTS: CIMP-high (≥5 methylated loci) and concurrent methylation in NEUROG1 and CDKN2A (p16) were found in 5.8 and 7.9 % of patients, respectively. Although CIMP-high status was not associated with survival, concurrent methylation in NEUROG1 and CDKN2A (p16) was associated with shorter OS and DFS. Moreover, the prognostic role of the concurrent methylation was different among sex. The negative prognostic impact was only observed in male but not in female (interaction p value = 0.026 for OS and 0.011 for DFS). In male, the 5-year OS was 61.6 % in concurrent methylation (+) and 91.7 % in concurrent methylation (−) (p < 0.001) whereas it was 95.0 and 92.8 % in female, respectively (p = 0.78). CONCLUSIONS: Concurrent methylation in NEUROG1 and CDKN2A is associated with poor survival in CRC treated with adjuvant FOLFOX. Interaction analysis indicates that the prognostic role is different according to sex. BioMed Central 2015-07-09 /pmc/articles/PMC4495938/ /pubmed/26157509 http://dx.doi.org/10.1186/s13148-015-0106-0 Text en © Lee et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lee, Dae-Won
Han, Sae-Won
Cha, Yongjun
Rhee, Ye Young
Bae, Jeong Mo
Cho, Nam-Yun
Lee, Kyung-Hun
Kim, Tae-Yong
Oh, Do-Youn
Im, Seock-Ah
Bang, Yung-Jue
Jeong, Seung-Yong
Park, Kyu Joo
Kang, Gyeong Hoon
Kim, Tae-You
Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX
title Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX
title_full Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX
title_fullStr Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX
title_full_unstemmed Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX
title_short Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX
title_sort different prognostic effect of cpg island methylation according to sex in colorectal cancer patients treated with adjuvant folfox
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495938/
https://www.ncbi.nlm.nih.gov/pubmed/26157509
http://dx.doi.org/10.1186/s13148-015-0106-0
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