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Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis
BACKGROUND: Previous approaches to defining subtypes of colorectal carcinoma (CRC) and other cancers based on transcriptomes have assumed the existence of discrete subtypes. We analyze gene expression patterns of colorectal tumors from a large number of patients to test this assumption and propose a...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154428/ https://www.ncbi.nlm.nih.gov/pubmed/30253799 http://dx.doi.org/10.1186/s13059-018-1511-4 |
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author | Ma, Siyuan Ogino, Shuji Parsana, Princy Nishihara, Reiko Qian, Zhirong Shen, Jeanne Mima, Kosuke Masugi, Yohei Cao, Yin Nowak, Jonathan A. Shima, Kaori Hoshida, Yujin Giovannucci, Edward L. Gala, Manish K. Chan, Andrew T. Fuchs, Charles S. Parmigiani, Giovanni Huttenhower, Curtis Waldron, Levi |
author_facet | Ma, Siyuan Ogino, Shuji Parsana, Princy Nishihara, Reiko Qian, Zhirong Shen, Jeanne Mima, Kosuke Masugi, Yohei Cao, Yin Nowak, Jonathan A. Shima, Kaori Hoshida, Yujin Giovannucci, Edward L. Gala, Manish K. Chan, Andrew T. Fuchs, Charles S. Parmigiani, Giovanni Huttenhower, Curtis Waldron, Levi |
author_sort | Ma, Siyuan |
collection | PubMed |
description | BACKGROUND: Previous approaches to defining subtypes of colorectal carcinoma (CRC) and other cancers based on transcriptomes have assumed the existence of discrete subtypes. We analyze gene expression patterns of colorectal tumors from a large number of patients to test this assumption and propose an approach to identify potentially a continuum of subtypes that are present across independent studies and cohorts. RESULTS: We examine the assumption of discrete CRC subtypes by integrating 18 published gene expression datasets and > 3700 patients, and contrary to previous reports, find no evidence to support the existence of discrete transcriptional subtypes. Using a meta-analysis approach to identify co-expression patterns present in multiple datasets, we identify and define robust, continuously varying subtype scores to represent CRC transcriptomes. The subtype scores are consistent with established subtypes (including microsatellite instability and previously proposed discrete transcriptome subtypes), but better represent overall transcriptional activity than do discrete subtypes. The scores are also better predictors of tumor location, stage, grade, and times of disease-free survival than discrete subtypes. Gene set enrichment analysis reveals that the subtype scores characterize T-cell function, inflammation response, and cyclin-dependent kinase regulation of DNA replication. CONCLUSIONS: We find no evidence to support discrete subtypes of the CRC transcriptome and instead propose two validated scores to better characterize a continuity of CRC transcriptomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-018-1511-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6154428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61544282018-09-26 Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis Ma, Siyuan Ogino, Shuji Parsana, Princy Nishihara, Reiko Qian, Zhirong Shen, Jeanne Mima, Kosuke Masugi, Yohei Cao, Yin Nowak, Jonathan A. Shima, Kaori Hoshida, Yujin Giovannucci, Edward L. Gala, Manish K. Chan, Andrew T. Fuchs, Charles S. Parmigiani, Giovanni Huttenhower, Curtis Waldron, Levi Genome Biol Research BACKGROUND: Previous approaches to defining subtypes of colorectal carcinoma (CRC) and other cancers based on transcriptomes have assumed the existence of discrete subtypes. We analyze gene expression patterns of colorectal tumors from a large number of patients to test this assumption and propose an approach to identify potentially a continuum of subtypes that are present across independent studies and cohorts. RESULTS: We examine the assumption of discrete CRC subtypes by integrating 18 published gene expression datasets and > 3700 patients, and contrary to previous reports, find no evidence to support the existence of discrete transcriptional subtypes. Using a meta-analysis approach to identify co-expression patterns present in multiple datasets, we identify and define robust, continuously varying subtype scores to represent CRC transcriptomes. The subtype scores are consistent with established subtypes (including microsatellite instability and previously proposed discrete transcriptome subtypes), but better represent overall transcriptional activity than do discrete subtypes. The scores are also better predictors of tumor location, stage, grade, and times of disease-free survival than discrete subtypes. Gene set enrichment analysis reveals that the subtype scores characterize T-cell function, inflammation response, and cyclin-dependent kinase regulation of DNA replication. CONCLUSIONS: We find no evidence to support discrete subtypes of the CRC transcriptome and instead propose two validated scores to better characterize a continuity of CRC transcriptomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-018-1511-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-25 /pmc/articles/PMC6154428/ /pubmed/30253799 http://dx.doi.org/10.1186/s13059-018-1511-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 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 Ma, Siyuan Ogino, Shuji Parsana, Princy Nishihara, Reiko Qian, Zhirong Shen, Jeanne Mima, Kosuke Masugi, Yohei Cao, Yin Nowak, Jonathan A. Shima, Kaori Hoshida, Yujin Giovannucci, Edward L. Gala, Manish K. Chan, Andrew T. Fuchs, Charles S. Parmigiani, Giovanni Huttenhower, Curtis Waldron, Levi Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis |
title | Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis |
title_full | Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis |
title_fullStr | Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis |
title_full_unstemmed | Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis |
title_short | Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis |
title_sort | continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154428/ https://www.ncbi.nlm.nih.gov/pubmed/30253799 http://dx.doi.org/10.1186/s13059-018-1511-4 |
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