An age stratified analysis of the biomarkers in patients with colorectal cancer

Abstract Colorectal cancer (CRC), a common malignant tumor of the digestive tract, has a high incidence and mortality rate. Several recent studies have found that aging is associated with the increasing risk of cancer. Nevertheless, the expression status and function of age-related genes in CRC is s...

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Autores principales:	Hui Yao, Chengjie Li, Xiaodong Tan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/91a4d4959aec47c48c5aa75eda30abb3
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spelling	oai:doaj.org-article:91a4d4959aec47c48c5aa75eda30abb32021-11-21T12:17:24ZAn age stratified analysis of the biomarkers in patients with colorectal cancer10.1038/s41598-021-01850-x2045-2322https://doaj.org/article/91a4d4959aec47c48c5aa75eda30abb32021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01850-xhttps://doaj.org/toc/2045-2322Abstract Colorectal cancer (CRC), a common malignant tumor of the digestive tract, has a high incidence and mortality rate. Several recent studies have found that aging is associated with the increasing risk of cancer. Nevertheless, the expression status and function of age-related genes in CRC is still not well understood. In the study, we comprehensively analyzed the gene expression data of CRC patients from The Cancer Genome Atlas (TCGA) database. Age-related differential expression genes (age-related DEGs) in tumor tissues compared with normal tissues of CRC were further identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of age-related DEGs were performed by clusterProfiler of R. Afterwards, we used the STRING database to map the protein–protein interaction network of DEGs. We constructed prognostic model through univariate and multivariate COX regression analyses, and further evaluated their predictive power. The prognostic gene signature-related functional pathways were explored by gene set enrichment analysis (GSEA). The weighted gene co-expression network analysis (WGCNA) was used to identify key module associated with two prognostic gene signatures. Finally, we used the Metascape to perform functional enrichment analysis of genes in the key module. A total of 279 age-related DEGs were identified from the TCGA database. GO and KEGG enrichment analysis showed that the age-related DEGs were enriched in the Modulation of chemical synaptic transmission and Neuroactive ligand–receptor interaction. Moreover, we established a novel age-related gene signature (DLX2 and PCOLCE2) for overall survival in CRC, which was further predicted in both the training and validation sets. The results of GSEA demonstrated that numerous disease-related pathways were enriched in the high-risk group. We identified 43 genes related to the DLX2 and PCOLCE2 by the WGCNA co-expression network. We also found that these 43 genes were enriched in the cancer-related pathways. To sum up, the study identified an age-related gene signature for predicting the prognosis of CRC patients, which is conducive to the identification of novel prognostic molecular markers.Hui YaoChengjie LiXiaodong TanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hui Yao Chengjie Li Xiaodong Tan An age stratified analysis of the biomarkers in patients with colorectal cancer
description	Abstract Colorectal cancer (CRC), a common malignant tumor of the digestive tract, has a high incidence and mortality rate. Several recent studies have found that aging is associated with the increasing risk of cancer. Nevertheless, the expression status and function of age-related genes in CRC is still not well understood. In the study, we comprehensively analyzed the gene expression data of CRC patients from The Cancer Genome Atlas (TCGA) database. Age-related differential expression genes (age-related DEGs) in tumor tissues compared with normal tissues of CRC were further identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of age-related DEGs were performed by clusterProfiler of R. Afterwards, we used the STRING database to map the protein–protein interaction network of DEGs. We constructed prognostic model through univariate and multivariate COX regression analyses, and further evaluated their predictive power. The prognostic gene signature-related functional pathways were explored by gene set enrichment analysis (GSEA). The weighted gene co-expression network analysis (WGCNA) was used to identify key module associated with two prognostic gene signatures. Finally, we used the Metascape to perform functional enrichment analysis of genes in the key module. A total of 279 age-related DEGs were identified from the TCGA database. GO and KEGG enrichment analysis showed that the age-related DEGs were enriched in the Modulation of chemical synaptic transmission and Neuroactive ligand–receptor interaction. Moreover, we established a novel age-related gene signature (DLX2 and PCOLCE2) for overall survival in CRC, which was further predicted in both the training and validation sets. The results of GSEA demonstrated that numerous disease-related pathways were enriched in the high-risk group. We identified 43 genes related to the DLX2 and PCOLCE2 by the WGCNA co-expression network. We also found that these 43 genes were enriched in the cancer-related pathways. To sum up, the study identified an age-related gene signature for predicting the prognosis of CRC patients, which is conducive to the identification of novel prognostic molecular markers.
format	article
author	Hui Yao Chengjie Li Xiaodong Tan
author_facet	Hui Yao Chengjie Li Xiaodong Tan
author_sort	Hui Yao
title	An age stratified analysis of the biomarkers in patients with colorectal cancer
title_short	An age stratified analysis of the biomarkers in patients with colorectal cancer
title_full	An age stratified analysis of the biomarkers in patients with colorectal cancer
title_fullStr	An age stratified analysis of the biomarkers in patients with colorectal cancer
title_full_unstemmed	An age stratified analysis of the biomarkers in patients with colorectal cancer
title_sort	age stratified analysis of the biomarkers in patients with colorectal cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/91a4d4959aec47c48c5aa75eda30abb3
work_keys_str_mv	AT huiyao anagestratifiedanalysisofthebiomarkersinpatientswithcolorectalcancer AT chengjieli anagestratifiedanalysisofthebiomarkersinpatientswithcolorectalcancer AT xiaodongtan anagestratifiedanalysisofthebiomarkersinpatientswithcolorectalcancer AT huiyao agestratifiedanalysisofthebiomarkersinpatientswithcolorectalcancer AT chengjieli agestratifiedanalysisofthebiomarkersinpatientswithcolorectalcancer AT xiaodongtan agestratifiedanalysisofthebiomarkersinpatientswithcolorectalcancer
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An age stratified analysis of the biomarkers in patients with colorectal cancer

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