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Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma

Lung cancer is a leading global cause of cancer‐related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression d...

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Published in:FEBS open bio 2019-02, Vol.9 (2), p.315-327
Main Authors: Ren, Zhi‐Peng, Hou, Xiao‐Bin, Tian, Xiao‐Dong, Guo, Jun‐Tang, Zhang, Lian‐Bin, Xue, Zhi‐Qiang, Deng, Jian‐Qing, Zhang, Shao‐Wei, Pan, Jun‐Yi, Chu, Xiang‐Yang
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container_title FEBS open bio
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creator Ren, Zhi‐Peng
Hou, Xiao‐Bin
Tian, Xiao‐Dong
Guo, Jun‐Tang
Zhang, Lian‐Bin
Xue, Zhi‐Qiang
Deng, Jian‐Qing
Zhang, Shao‐Wei
Pan, Jun‐Yi
Chu, Xiang‐Yang
description Lung cancer is a leading global cause of cancer‐related death, and lung adenocarcinoma (LUAD) accounts for ~ 50% of lung cancer. Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real‐time PCR (qRT‐PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT‐PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD. We downloaded clinical data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas and identified 13 differentially expressed microRNAs (DEmiRNAs), 2301 differentially expressed mRNAs (DEmRNAs), and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues. We identified nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value.
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Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real‐time PCR (qRT‐PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT‐PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD. We downloaded clinical data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas and identified 13 differentially expressed microRNAs (DEmiRNAs), 2301 differentially expressed mRNAs (DEmRNAs), and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues. We identified nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value.</description><identifier>ISSN: 2211-5463</identifier><identifier>EISSN: 2211-5463</identifier><identifier>DOI: 10.1002/2211-5463.12572</identifier><identifier>PMID: 30761256</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>Adenocarcinoma of Lung - diagnosis ; Adenocarcinoma of Lung - genetics ; biomarker ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - genetics ; Databases, Genetic ; DEmiRNA ; Gene Regulatory Networks - genetics ; Humans ; LUAD ; lung adenocarcinoma ; Lung Neoplasms - diagnosis ; Lung Neoplasms - genetics ; microRNA ; MicroRNAs - analysis ; MicroRNAs - genetics ; TCGA</subject><ispartof>FEBS open bio, 2019-02, Vol.9 (2), p.315-327</ispartof><rights>2018 The Authors. 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Here, we screened for novel and specific biomarkers of LUAD by searching for differentially expressed mRNAs (DEmRNAs) and microRNAs (DEmiRNAs) in LUAD patient expression data within The Cancer Genome Atlas (TCGA). The identified optimal diagnostic miRNA biomarkers were used to establish classification models (including support vector machine, decision tree, and random forest) to distinguish between LUAD and adjacent tissues. We then predicted the targets of identified optimal diagnostic miRNA biomarkers, functionally annotated these target genes, and performed receiver operating characteristic curve analysis of the respective DEmiRNA biomarkers, their target DEmRNAs, and combinations of DEmiRNA biomarkers. We validated the expression of selected DEmiRNA biomarkers by quantitative real‐time PCR (qRT‐PCR). In all, we identified a total of 13 DEmiRNAs, 2301 DEmRNAs and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues and selected nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value. The predicted targets of these nine DEmiRNAs were significantly enriched in transcriptional misregulation in cancer and central carbon metabolism. Our qRT‐PCR results were generally consistent with our integrated analysis. In summary, our study identified nine DEmiRNAs that may serve as potential diagnostic biomarkers of LUAD. Functional annotation of their target DEmRNAs may provide information on their roles in LUAD. We downloaded clinical data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas and identified 13 differentially expressed microRNAs (DEmiRNAs), 2301 differentially expressed mRNAs (DEmRNAs), and 232 DEmiRNA–target DEmRNA pairs between LUAD and adjacent tissues. We identified nine DEmiRNAs (hsa‐mir‐486‐1, hsa‐mir‐486‐2, hsa‐mir‐153, hsa‐mir‐210, hsa‐mir‐9‐1, hsa‐mir‐9‐2, hsa‐mir‐9‐3, hsa‐mir‐577, and hsa‐mir‐4732) as optimal LUAD‐specific biomarkers with great diagnostic value.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>30761256</pmid><doi>10.1002/2211-5463.12572</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma of Lung - diagnosis
Adenocarcinoma of Lung - genetics
biomarker
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Databases, Genetic
DEmiRNA
Gene Regulatory Networks - genetics
Humans
LUAD
lung adenocarcinoma
Lung Neoplasms - diagnosis
Lung Neoplasms - genetics
microRNA
MicroRNAs - analysis
MicroRNAs - genetics
TCGA
title Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma
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