Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysis

Abstract Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers types and can function as competing endogenous RNAs (ceRNAs), which promote and maintain tumor initiation and progression. In this study, we explored the functional roles and regulatory mechanisms of lncRNAs as ceRNAs...

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Main Authors: Hui Zhang, Zhuo Wang, Jianzhong Wu, Rong Ma, Jifeng Feng
Format: Article
Language:English
Published: Wiley 2019-03-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.1813
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author Hui Zhang
Zhuo Wang
Jianzhong Wu
Rong Ma
Jifeng Feng
author_facet Hui Zhang
Zhuo Wang
Jianzhong Wu
Rong Ma
Jifeng Feng
author_sort Hui Zhang
collection DOAJ
description Abstract Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers types and can function as competing endogenous RNAs (ceRNAs), which promote and maintain tumor initiation and progression. In this study, we explored the functional roles and regulatory mechanisms of lncRNAs as ceRNAs in colorectal cancer and their clinical potential as biomarkers. The RNA sequencing profiles of patients with colorectal cancer were downloaded from TCGA database, and 62 lncRNAs, 30miRNAs, and 59 mRNAs were identified to comprise the ceRNA network (fold change > 2, P < 0.01). Functional enrichment analysis suggested that the target genes of the ceRNA network may be involved in the pathways related to cancer, including the signaling pathway that regulates the pluripotency of stem cells, wnt signaling pathway, hippo signaling pathway, basal cell carcinoma, and colorectal cancer. Univariate and multivariate Cox's proportional hazard regression model revealed that five (H19, MIR31HG, HOTAIR, WT1‐AS, and LINC00488) out of 62 lncRNAs were closely related to the overall survival (OS) (P < 0.05). Furthermore, the five‐lncRNA model could be an independent prognostic model in colorectal cancer. We computed for the risk function and constructed a risk score based on the five lncRNAs. Results showed that patients with high‐risk scores have poor survival rates. Additionally, combing the risk score and other clinicopathological features, we can better predict the patient's survival probabilities. Furthermore, we validate our model in the GSE38832 dataset. Collectively, our study has provided a deeper understanding of the lncRNA‐related ceRNA regulatory mechanism in CRC and identified five‐lncRNA model, which could be considered as candidate prognostic biomarkers and therapeutic targets.
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spelling doaj-art-0d06a49f68e64391af1f2ce25515ed002025-01-31T08:47:42ZengWileyCancer Medicine2045-76342019-03-018386387310.1002/cam4.1813Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysisHui Zhang0Zhuo Wang1Jianzhong Wu2Rong Ma3Jifeng Feng4The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital Nanjing Jiangsu ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital Nanjing Jiangsu ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital Nanjing Jiangsu ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital Nanjing Jiangsu ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital Nanjing Jiangsu ChinaAbstract Long noncoding RNAs (lncRNAs) are aberrantly expressed in various cancers types and can function as competing endogenous RNAs (ceRNAs), which promote and maintain tumor initiation and progression. In this study, we explored the functional roles and regulatory mechanisms of lncRNAs as ceRNAs in colorectal cancer and their clinical potential as biomarkers. The RNA sequencing profiles of patients with colorectal cancer were downloaded from TCGA database, and 62 lncRNAs, 30miRNAs, and 59 mRNAs were identified to comprise the ceRNA network (fold change > 2, P < 0.01). Functional enrichment analysis suggested that the target genes of the ceRNA network may be involved in the pathways related to cancer, including the signaling pathway that regulates the pluripotency of stem cells, wnt signaling pathway, hippo signaling pathway, basal cell carcinoma, and colorectal cancer. Univariate and multivariate Cox's proportional hazard regression model revealed that five (H19, MIR31HG, HOTAIR, WT1‐AS, and LINC00488) out of 62 lncRNAs were closely related to the overall survival (OS) (P < 0.05). Furthermore, the five‐lncRNA model could be an independent prognostic model in colorectal cancer. We computed for the risk function and constructed a risk score based on the five lncRNAs. Results showed that patients with high‐risk scores have poor survival rates. Additionally, combing the risk score and other clinicopathological features, we can better predict the patient's survival probabilities. Furthermore, we validate our model in the GSE38832 dataset. Collectively, our study has provided a deeper understanding of the lncRNA‐related ceRNA regulatory mechanism in CRC and identified five‐lncRNA model, which could be considered as candidate prognostic biomarkers and therapeutic targets.https://doi.org/10.1002/cam4.1813ceRNAcolorectal cancerlncRNAprognostic biomarker
spellingShingle Hui Zhang
Zhuo Wang
Jianzhong Wu
Rong Ma
Jifeng Feng
Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysis
Cancer Medicine
ceRNA
colorectal cancer
lncRNA
prognostic biomarker
title Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysis
title_full Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysis
title_fullStr Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysis
title_full_unstemmed Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysis
title_short Long noncoding RNAs predict the survival of patients with colorectal cancer as revealed by constructing an endogenous RNA network using bioinformation analysis
title_sort long noncoding rnas predict the survival of patients with colorectal cancer as revealed by constructing an endogenous rna network using bioinformation analysis
topic ceRNA
colorectal cancer
lncRNA
prognostic biomarker
url https://doi.org/10.1002/cam4.1813
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AT zhuowang longnoncodingrnaspredictthesurvivalofpatientswithcolorectalcancerasrevealedbyconstructinganendogenousrnanetworkusingbioinformationanalysis
AT jianzhongwu longnoncodingrnaspredictthesurvivalofpatientswithcolorectalcancerasrevealedbyconstructinganendogenousrnanetworkusingbioinformationanalysis
AT rongma longnoncodingrnaspredictthesurvivalofpatientswithcolorectalcancerasrevealedbyconstructinganendogenousrnanetworkusingbioinformationanalysis
AT jifengfeng longnoncodingrnaspredictthesurvivalofpatientswithcolorectalcancerasrevealedbyconstructinganendogenousrnanetworkusingbioinformationanalysis