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A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer

Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for pr...

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Autores principales: Kim, Seon-Kyu, Kim, Seon-Young, Kim, Chan Wook, Roh, Seon Ae, Ha, Ye Jin, Lee, Jong Lyul, Heo, Haejeong, Cho, Dong-Hyung, Lee, Ju-Seog, Kim, Yong Sung, Kim, Jin Cheon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802642/
https://www.ncbi.nlm.nih.gov/pubmed/31578316
http://dx.doi.org/10.1038/s12276-019-0319-y
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author Kim, Seon-Kyu
Kim, Seon-Young
Kim, Chan Wook
Roh, Seon Ae
Ha, Ye Jin
Lee, Jong Lyul
Heo, Haejeong
Cho, Dong-Hyung
Lee, Ju-Seog
Kim, Yong Sung
Kim, Jin Cheon
author_facet Kim, Seon-Kyu
Kim, Seon-Young
Kim, Chan Wook
Roh, Seon Ae
Ha, Ye Jin
Lee, Jong Lyul
Heo, Haejeong
Cho, Dong-Hyung
Lee, Ju-Seog
Kim, Yong Sung
Kim, Jin Cheon
author_sort Kim, Seon-Kyu
collection PubMed
description Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for precisely predicting CRC heterogeneity. We performed transcriptomic profiling using RNA-seq data generated from the primary tissue samples of 130 CRC patients. A prognostic index (PI) based on recurrence-associated genes was developed and validated in two larger independent CRC patient cohorts (n = 795). The association between the PI and prognosis of CRC patients was evaluated using Kaplan–Meier plots, log-rank tests, a Cox regression analysis and a RT-PCR analysis. Transcriptomic profiling in 130 CRC patients identified two distinct subtypes associated with systemic recurrence. Pathway enrichment and RT-PCR analyses revealed an eleven gene signature incorporated into the PI system, which was a significant prognostic indicator of CRC. Multivariate and subset analyses showed that PI was an independent risk factor (HR = 1.812, 95% CI = 1.342–2.448, P < 0.001) with predictive value to identify low-risk stage II patients who responded the worst to adjuvant chemotherapy. Finally, a comparative analysis with previously reported Consensus Molecular Subgroup (CMS), high-risk patients classified by the PI revealed a distinct molecular property similar to CMS4, associated with a poor prognosis. This novel PI predictor based on an eleven gene signature likely represents a surrogate diagnostic tool for identifying high-risk CRC patients and for predicting the worst responding patients for adjuvant chemotherapy.
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spelling pubmed-68026422019-10-24 A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer Kim, Seon-Kyu Kim, Seon-Young Kim, Chan Wook Roh, Seon Ae Ha, Ye Jin Lee, Jong Lyul Heo, Haejeong Cho, Dong-Hyung Lee, Ju-Seog Kim, Yong Sung Kim, Jin Cheon Exp Mol Med Article Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for precisely predicting CRC heterogeneity. We performed transcriptomic profiling using RNA-seq data generated from the primary tissue samples of 130 CRC patients. A prognostic index (PI) based on recurrence-associated genes was developed and validated in two larger independent CRC patient cohorts (n = 795). The association between the PI and prognosis of CRC patients was evaluated using Kaplan–Meier plots, log-rank tests, a Cox regression analysis and a RT-PCR analysis. Transcriptomic profiling in 130 CRC patients identified two distinct subtypes associated with systemic recurrence. Pathway enrichment and RT-PCR analyses revealed an eleven gene signature incorporated into the PI system, which was a significant prognostic indicator of CRC. Multivariate and subset analyses showed that PI was an independent risk factor (HR = 1.812, 95% CI = 1.342–2.448, P < 0.001) with predictive value to identify low-risk stage II patients who responded the worst to adjuvant chemotherapy. Finally, a comparative analysis with previously reported Consensus Molecular Subgroup (CMS), high-risk patients classified by the PI revealed a distinct molecular property similar to CMS4, associated with a poor prognosis. This novel PI predictor based on an eleven gene signature likely represents a surrogate diagnostic tool for identifying high-risk CRC patients and for predicting the worst responding patients for adjuvant chemotherapy. Nature Publishing Group UK 2019-10-02 /pmc/articles/PMC6802642/ /pubmed/31578316 http://dx.doi.org/10.1038/s12276-019-0319-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Seon-Kyu
Kim, Seon-Young
Kim, Chan Wook
Roh, Seon Ae
Ha, Ye Jin
Lee, Jong Lyul
Heo, Haejeong
Cho, Dong-Hyung
Lee, Ju-Seog
Kim, Yong Sung
Kim, Jin Cheon
A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
title A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
title_full A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
title_fullStr A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
title_full_unstemmed A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
title_short A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
title_sort prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802642/
https://www.ncbi.nlm.nih.gov/pubmed/31578316
http://dx.doi.org/10.1038/s12276-019-0319-y
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