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Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence
Colorectal cancer (CRC) is the fourth-ranked cause of cancer-related deaths worldwide. Despite recent advances in CRC management, distant recurrence (DR) remains the major cause of mortality in patients with preoperative chemotherapy and radiotherapy, underscoring a need to precisely identify novel...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147898/ https://www.ncbi.nlm.nih.gov/pubmed/27935967 http://dx.doi.org/10.1371/journal.pone.0167455 |
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author | Alajez, Nehad M. |
author_facet | Alajez, Nehad M. |
author_sort | Alajez, Nehad M. |
collection | PubMed |
description | Colorectal cancer (CRC) is the fourth-ranked cause of cancer-related deaths worldwide. Despite recent advances in CRC management, distant recurrence (DR) remains the major cause of mortality in patients with preoperative chemotherapy and radiotherapy, underscoring a need to precisely identify novel gene signatures for predicting the risk of systemic relapse. Herein, we integrated two independent CRC gene expression datasets: the GSE71222 dataset, including 26 patients who developed DR and 126 patients who did not develop DR, and the GSE21510 dataset, including 23 patients who developed DR and 76 patients who did not develop DR. Our data revealed 37 common upregulated genes (fold change (FC) ≥ 1.5, P < 0.05) and three common downregulated genes (FC ≤ 1.5, P < 0.05) between DR and non-recurrent patients from the two datasets. We subsequently validated the upregulated gene panel in the Cancer Genome Atlas CRC datasets (379 patients), which identified a five-gene signature (S100A2, VIP, HOXC6, DACT1, KIF26B) associated with poor overall survival (OS, log-rank test P-value: 1.19 × 10(−4)) and poor disease-free survival (DFS, log-rank test P-value: 0.002). In a Cox proportional hazards multiple regression model, the five-gene signature and tumor stage retained their significance as independent prognostic factors for CRC DFS and OS. Therefore, our data identified a novel DR gene expression signature associated with worse prognosis in CRC. |
format | Online Article Text |
id | pubmed-5147898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51478982016-12-28 Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence Alajez, Nehad M. PLoS One Research Article Colorectal cancer (CRC) is the fourth-ranked cause of cancer-related deaths worldwide. Despite recent advances in CRC management, distant recurrence (DR) remains the major cause of mortality in patients with preoperative chemotherapy and radiotherapy, underscoring a need to precisely identify novel gene signatures for predicting the risk of systemic relapse. Herein, we integrated two independent CRC gene expression datasets: the GSE71222 dataset, including 26 patients who developed DR and 126 patients who did not develop DR, and the GSE21510 dataset, including 23 patients who developed DR and 76 patients who did not develop DR. Our data revealed 37 common upregulated genes (fold change (FC) ≥ 1.5, P < 0.05) and three common downregulated genes (FC ≤ 1.5, P < 0.05) between DR and non-recurrent patients from the two datasets. We subsequently validated the upregulated gene panel in the Cancer Genome Atlas CRC datasets (379 patients), which identified a five-gene signature (S100A2, VIP, HOXC6, DACT1, KIF26B) associated with poor overall survival (OS, log-rank test P-value: 1.19 × 10(−4)) and poor disease-free survival (DFS, log-rank test P-value: 0.002). In a Cox proportional hazards multiple regression model, the five-gene signature and tumor stage retained their significance as independent prognostic factors for CRC DFS and OS. Therefore, our data identified a novel DR gene expression signature associated with worse prognosis in CRC. Public Library of Science 2016-12-09 /pmc/articles/PMC5147898/ /pubmed/27935967 http://dx.doi.org/10.1371/journal.pone.0167455 Text en © 2016 Nehad M. Alajez http://creativecommons.org/licenses/by/4.0/ 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 author and source are credited. |
spellingShingle | Research Article Alajez, Nehad M. Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence |
title | Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence |
title_full | Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence |
title_fullStr | Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence |
title_full_unstemmed | Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence |
title_short | Large-Scale Analysis of Gene Expression Data Reveals a Novel Gene Expression Signature Associated with Colorectal Cancer Distant Recurrence |
title_sort | large-scale analysis of gene expression data reveals a novel gene expression signature associated with colorectal cancer distant recurrence |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147898/ https://www.ncbi.nlm.nih.gov/pubmed/27935967 http://dx.doi.org/10.1371/journal.pone.0167455 |
work_keys_str_mv | AT alajeznehadm largescaleanalysisofgeneexpressiondatarevealsanovelgeneexpressionsignatureassociatedwithcolorectalcancerdistantrecurrence |