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Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival

The prognosis for patients with gastric cancer (GC) is usually poor, as the majority of patients have reached the advanced stages of disease at the point of diagnosis. Therefore, revealing the mechanisms of GC is necessary for the identification of key biomarkers and the development of effective tar...

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Autores principales: Hu, Zunqi, Yang, Dejun, Tang, Yuan, Zhang, Xin, Wei, Ziran, Fu, Hongbing, Xu, Jiapeng, Zhu, Zhenxin, Cai, Qingping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447923/
https://www.ncbi.nlm.nih.gov/pubmed/30988816
http://dx.doi.org/10.3892/ol.2019.10124
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author Hu, Zunqi
Yang, Dejun
Tang, Yuan
Zhang, Xin
Wei, Ziran
Fu, Hongbing
Xu, Jiapeng
Zhu, Zhenxin
Cai, Qingping
author_facet Hu, Zunqi
Yang, Dejun
Tang, Yuan
Zhang, Xin
Wei, Ziran
Fu, Hongbing
Xu, Jiapeng
Zhu, Zhenxin
Cai, Qingping
author_sort Hu, Zunqi
collection PubMed
description The prognosis for patients with gastric cancer (GC) is usually poor, as the majority of patients have reached the advanced stages of disease at the point of diagnosis. Therefore, revealing the mechanisms of GC is necessary for the identification of key biomarkers and the development of effective targeted therapies. The present study aimed to identify long non-coding RNAs (lncRNAs) prominently expressed in patients with GC. The GC dataset (including 384 GC samples) was downloaded from The Cancer Genome Atlas database as the training set. A number of other GC datasets were obtained from the Gene Expression Omnibus database as validation sets. Following data processing, lncRNAs were annotated, followed by co-expression module analysis to identify stable modules, using the weighted gene co-expression network analysis (WGCNA) package. Prognosis-associated lncRNAs were screened using the ‘survival’ package. Following the selection of the optimal lncRNA combinations using the ‘penalized’ package, risk score systems were constructed and assessed. Consensus differentially-expressed RNAs (DE-RNAs) were screened using the MetaDE package, and an lncRNA-mRNA network was constructed. Additionally, pathway enrichment analysis was conducted for the network nodes using gene set enrichment analysis (GSEA). A total of seven modules (blue, brown, green, grey, red, turquoise and yellow) were obtained following WGCNA analysis, among which the green and turquoise modules were stable and associated with the histological grade of GC. A total of 12 prognosis-associated lncRNAs were identified in the two modules. Combined with the optimal lncRNA combinations, risk score systems were constructed. The risk score system based on the green module [including ITPK1 antisense RNA 1 (ITPK1-AS1), KCNQ1 downstream neighbor (KCNQ1DN), long intergenic non-protein coding RNA 167 (LINC00167), LINC00173 and LINC00307] was the more efficient at predicting risk compared with those based on the turquoise, or the green + turquoise modules. A total of 1,105 consensus DE-RNAs were identified; GSEA revealed that LINC00167, LINC00173 and LINC00307 had the same association directions with 4 pathways and the 32 genes involved in those pathways. In conclusion, a risk score system based on the green module may be applied to predict the survival of patients with GC. Furthermore, ITPK1-AS1, KCNQ1DN, LINC00167, LINC00173 and LINC00307 may serve as biomarkers for GC pathogenesis.
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spelling pubmed-64479232019-04-15 Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival Hu, Zunqi Yang, Dejun Tang, Yuan Zhang, Xin Wei, Ziran Fu, Hongbing Xu, Jiapeng Zhu, Zhenxin Cai, Qingping Oncol Lett Articles The prognosis for patients with gastric cancer (GC) is usually poor, as the majority of patients have reached the advanced stages of disease at the point of diagnosis. Therefore, revealing the mechanisms of GC is necessary for the identification of key biomarkers and the development of effective targeted therapies. The present study aimed to identify long non-coding RNAs (lncRNAs) prominently expressed in patients with GC. The GC dataset (including 384 GC samples) was downloaded from The Cancer Genome Atlas database as the training set. A number of other GC datasets were obtained from the Gene Expression Omnibus database as validation sets. Following data processing, lncRNAs were annotated, followed by co-expression module analysis to identify stable modules, using the weighted gene co-expression network analysis (WGCNA) package. Prognosis-associated lncRNAs were screened using the ‘survival’ package. Following the selection of the optimal lncRNA combinations using the ‘penalized’ package, risk score systems were constructed and assessed. Consensus differentially-expressed RNAs (DE-RNAs) were screened using the MetaDE package, and an lncRNA-mRNA network was constructed. Additionally, pathway enrichment analysis was conducted for the network nodes using gene set enrichment analysis (GSEA). A total of seven modules (blue, brown, green, grey, red, turquoise and yellow) were obtained following WGCNA analysis, among which the green and turquoise modules were stable and associated with the histological grade of GC. A total of 12 prognosis-associated lncRNAs were identified in the two modules. Combined with the optimal lncRNA combinations, risk score systems were constructed. The risk score system based on the green module [including ITPK1 antisense RNA 1 (ITPK1-AS1), KCNQ1 downstream neighbor (KCNQ1DN), long intergenic non-protein coding RNA 167 (LINC00167), LINC00173 and LINC00307] was the more efficient at predicting risk compared with those based on the turquoise, or the green + turquoise modules. A total of 1,105 consensus DE-RNAs were identified; GSEA revealed that LINC00167, LINC00173 and LINC00307 had the same association directions with 4 pathways and the 32 genes involved in those pathways. In conclusion, a risk score system based on the green module may be applied to predict the survival of patients with GC. Furthermore, ITPK1-AS1, KCNQ1DN, LINC00167, LINC00173 and LINC00307 may serve as biomarkers for GC pathogenesis. D.A. Spandidos 2019-05 2019-03-08 /pmc/articles/PMC6447923/ /pubmed/30988816 http://dx.doi.org/10.3892/ol.2019.10124 Text en Copyright: © Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Hu, Zunqi
Yang, Dejun
Tang, Yuan
Zhang, Xin
Wei, Ziran
Fu, Hongbing
Xu, Jiapeng
Zhu, Zhenxin
Cai, Qingping
Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival
title Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival
title_full Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival
title_fullStr Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival
title_full_unstemmed Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival
title_short Five-long non-coding RNA risk score system for the effective prediction of gastric cancer patient survival
title_sort five-long non-coding rna risk score system for the effective prediction of gastric cancer patient survival
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447923/
https://www.ncbi.nlm.nih.gov/pubmed/30988816
http://dx.doi.org/10.3892/ol.2019.10124
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