Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.

<h4>Background</h4>Liver metastases are the major cause of colorectal cancer (CRC)-related deaths. However, there is no reliable clinical predictor for CRC progression to liver metastasis. In this study, we investigated possible predictors (miRNAs and biomarkers) for clinical application...

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Autores principales:	Precious Takondwa Makondi, Po-Li Wei, Chien-Yu Huang, Yu-Jia Chang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b6df19c100a4184990a818ea25e967b
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spelling	oai:doaj.org-article:3b6df19c100a4184990a818ea25e967b2021-12-02T20:15:52ZDevelopment of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.1932-620310.1371/journal.pone.0211968https://doaj.org/article/3b6df19c100a4184990a818ea25e967b2019-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0211968https://doaj.org/toc/1932-6203<h4>Background</h4>Liver metastases are the major cause of colorectal cancer (CRC)-related deaths. However, there is no reliable clinical predictor for CRC progression to liver metastasis. In this study, we investigated possible predictors (miRNAs and biomarkers) for clinical application.<h4>Methodology</h4>The Gene Expression Omnibus (GEO) datasets GSE49355, GSE41258 and GSE81558 for genes and GSE54088 and GSE56350 for miRNAs were used to identify common differentially expressed genes (DEGs) and miRNAs between primary CRC tissues and liver metastases. The identified miRNAs and their targets from the DEGs were verified in datasets comprising gene, miRNA and miRNA exosome profiles of CRC patients with no distant metastases (M0) and distant metastases (M1); the interaction networks and pathways were also mapped.<h4>Results</h4>There were 49 upregulated and 13 downregulated DEGs and 16 downregulated and 14 upregulated miRNAs; between the DEGs and miRNA targets, there were five upregulated and four downregulated genes. MiR-20a was strongly correlated with the status of liver metastasis. MiR-20a, miR499a, and miR-576-5p were highly correlated with the metastatic outcomes. MiR-20a was significantly highly expressed in the M1 group. In an analysis of the miRNA target genes, we found that CDH2, KNG1, and MMP2 were correlated with CRC metastasis. We demonstrated a new possible pathway for CRC metastasis: miR-576-5p/F9, miR20a/MMP2, CTSK, MMP3, and miR449a/P2RY14. The regulation of IGF transport and uptake by IGFBPs, extracellular matrix organization, signal transduction and the immune system were the enriched pathways.<h4>Conclusion</h4>This model can predict CRC to liver metastases and the pathways involved, which can be clinically applicable.Precious Takondwa MakondiPo-Li WeiChien-Yu HuangYu-Jia ChangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 14, Iss 2, p e0211968 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Precious Takondwa Makondi Po-Li Wei Chien-Yu Huang Yu-Jia Chang Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.
description	<h4>Background</h4>Liver metastases are the major cause of colorectal cancer (CRC)-related deaths. However, there is no reliable clinical predictor for CRC progression to liver metastasis. In this study, we investigated possible predictors (miRNAs and biomarkers) for clinical application.<h4>Methodology</h4>The Gene Expression Omnibus (GEO) datasets GSE49355, GSE41258 and GSE81558 for genes and GSE54088 and GSE56350 for miRNAs were used to identify common differentially expressed genes (DEGs) and miRNAs between primary CRC tissues and liver metastases. The identified miRNAs and their targets from the DEGs were verified in datasets comprising gene, miRNA and miRNA exosome profiles of CRC patients with no distant metastases (M0) and distant metastases (M1); the interaction networks and pathways were also mapped.<h4>Results</h4>There were 49 upregulated and 13 downregulated DEGs and 16 downregulated and 14 upregulated miRNAs; between the DEGs and miRNA targets, there were five upregulated and four downregulated genes. MiR-20a was strongly correlated with the status of liver metastasis. MiR-20a, miR499a, and miR-576-5p were highly correlated with the metastatic outcomes. MiR-20a was significantly highly expressed in the M1 group. In an analysis of the miRNA target genes, we found that CDH2, KNG1, and MMP2 were correlated with CRC metastasis. We demonstrated a new possible pathway for CRC metastasis: miR-576-5p/F9, miR20a/MMP2, CTSK, MMP3, and miR449a/P2RY14. The regulation of IGF transport and uptake by IGFBPs, extracellular matrix organization, signal transduction and the immune system were the enriched pathways.<h4>Conclusion</h4>This model can predict CRC to liver metastases and the pathways involved, which can be clinically applicable.
format	article
author	Precious Takondwa Makondi Po-Li Wei Chien-Yu Huang Yu-Jia Chang
author_facet	Precious Takondwa Makondi Po-Li Wei Chien-Yu Huang Yu-Jia Chang
author_sort	Precious Takondwa Makondi
title	Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.
title_short	Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.
title_full	Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.
title_fullStr	Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.
title_full_unstemmed	Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.
title_sort	development of novel predictive mirna/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.
publisher	Public Library of Science (PLoS)
publishDate	2019
url	https://doaj.org/article/3b6df19c100a4184990a818ea25e967b
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Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach.

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