Five microRNAs in plasma as novel biomarkers for screening of early-stage non-small cell lung cancer

In order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC. In training set, 25 ea...

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Veröffentlicht in:Respiratory research 2014-11, Vol.15 (1), p.149-149, Article 149
Hauptverfasser: Geng, Qing, Fan, Tao, Zhang, Boyou, Wang, Wei, Xu, Yao, Hu, Hao
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Fan, Tao
Zhang, Boyou
Wang, Wei
Xu, Yao
Hu, Hao
description In order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC. In training set, 25 early-stage NSCLC patients and 25 matched healthy controls are included to assess the miRNA expression profile between early-stage NSCLC patients and healthy controls by real-time RT-PCR. We found that five of these miRNAs (miR-20a, miR-223, miR-21, miR-221 and miR-145) levels in NSCLC patients were significantly dysregulated compared with the healthy groups and thus were selected to validation set. Therefore, a validation experiment was further performed to investigate the potential predictive power of these five miRNAs based on 126 early-stage NSCLC patients, 42 NCPD patients and 60 healthy controls. The receiver operating characteristic (ROC) curves were generated for the five miRNAs. ROC curve analyses suggested that these five plasma miRNAs could be promising biomarkers for NSCLC, with relatively high AUC values as follows: miR-20a, 0.89 with 95% CI of [0.85-0.93]; miR-223, 0.94 with 95% CI of [0.91-0.96]; miR-21, 0.77 with 95% CI of [0.71-0.83]; miR-155, 0.92 with 95% CI of [0.89-0.96]; miR-145, 0.77 with 95% CI of [0.71-0.83]. Stratified analyses indicated that plasma miR-20a, miR-223, miR-21 and miR-145 showed better predictive value in smokers than in non-smokers, while miR-155 might be more suitable for non-smokers. In addition, all of these five miRNAs could differentiate NSCLC from controls with a higher accuracy in advanced stage and squamous carcinoma subgroups. In conclusion, our study suggested that five plasma miRNAs (miR-20a, miR-145, miR-21, miR-223 and miR-221) can be used as promising biomarkers in early screening of NSCLC. Nevertheless, further validation and optimizing improvement should be performed on larger sample to confirm our results.
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In training set, 25 early-stage NSCLC patients and 25 matched healthy controls are included to assess the miRNA expression profile between early-stage NSCLC patients and healthy controls by real-time RT-PCR. We found that five of these miRNAs (miR-20a, miR-223, miR-21, miR-221 and miR-145) levels in NSCLC patients were significantly dysregulated compared with the healthy groups and thus were selected to validation set. Therefore, a validation experiment was further performed to investigate the potential predictive power of these five miRNAs based on 126 early-stage NSCLC patients, 42 NCPD patients and 60 healthy controls. The receiver operating characteristic (ROC) curves were generated for the five miRNAs. ROC curve analyses suggested that these five plasma miRNAs could be promising biomarkers for NSCLC, with relatively high AUC values as follows: miR-20a, 0.89 with 95% CI of [0.85-0.93]; miR-223, 0.94 with 95% CI of [0.91-0.96]; miR-21, 0.77 with 95% CI of [0.71-0.83]; miR-155, 0.92 with 95% CI of [0.89-0.96]; miR-145, 0.77 with 95% CI of [0.71-0.83]. Stratified analyses indicated that plasma miR-20a, miR-223, miR-21 and miR-145 showed better predictive value in smokers than in non-smokers, while miR-155 might be more suitable for non-smokers. In addition, all of these five miRNAs could differentiate NSCLC from controls with a higher accuracy in advanced stage and squamous carcinoma subgroups. In conclusion, our study suggested that five plasma miRNAs (miR-20a, miR-145, miR-21, miR-223 and miR-221) can be used as promising biomarkers in early screening of NSCLC. 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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Geng et al.; licensee BioMed Central Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-74554a90c0b533259095acfffc1990d43a52dc0ae5a02ea9f382d76f31f81fe93</citedby><cites>FETCH-LOGICAL-c560t-74554a90c0b533259095acfffc1990d43a52dc0ae5a02ea9f382d76f31f81fe93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248445/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248445/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25421010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Geng, Qing</creatorcontrib><creatorcontrib>Fan, Tao</creatorcontrib><creatorcontrib>Zhang, Boyou</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Xu, Yao</creatorcontrib><creatorcontrib>Hu, Hao</creatorcontrib><title>Five microRNAs in plasma as novel biomarkers for screening of early-stage non-small cell lung cancer</title><title>Respiratory research</title><addtitle>Respir Res</addtitle><description>In order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC. 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Nevertheless, further validation and optimizing improvement should be performed on larger sample to confirm our results.</description><subject>Accuracy</subject><subject>Analysis</subject><subject>Area Under Curve</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Carcinoma, Non-Small-Cell Lung - blood</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>Cell growth</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Comparative analysis</subject><subject>Diagnosis</subject><subject>Disease</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Genetic Testing - methods</subject><subject>Humans</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Lung Neoplasms - blood</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Materials selection</subject><subject>Medical imaging</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Neoplasm Staging</subject><subject>Plasma</subject><subject>Predictive Value of Tests</subject><subject>Reproducibility of Results</subject><subject>Risk Factors</subject><subject>ROC Curve</subject><subject>Studies</subject><subject>Surgery</subject><subject>Thoracic surgery</subject><issn>1465-993X</issn><issn>1465-9921</issn><issn>1465-993X</issn><issn>1465-9921</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptUl1rFDEUDaLYWv0BvkjAF1-m5nNm8iIspbVCURAF38LdzM2aOpOsyc5C_70Ztq2tSLhJSM45yUkOIa85O-W8b98XLozkDeNqKdPIJ-SYq1Y3xsgfTx_Mj8iLUq4Z413f6efkSGglOOPsmAwXYY90Ci6nr59XhYZItyOUCSgUGtMeR7oOaYL8C3OhPmVaXEaMIW5o8hQhjzdN2cEGKzo2lTiO1GHtxrlCHESH-SV55mEs-Op2PCHfL86_nV02V18-fjpbXTVOt2zXdEprBYY5ttZSCm2Y0eC8944bwwYlQYvBMUANTCAYL3sxdK2X3Pfco5En5MNBdzuvJxwcxl2G0W5zqAZubIJgH-_E8NNu0t4qoXqldBV4dyuQ0-8Zy85OoSxuIGKai-Vt10rZa8Yq9O0_0Os051jtVZQwqjOd7v6iNjCiDdGneq5bRO1KS9Ny1Zvl3qf_QdU2YP2ZFNGHuv6IwA-E-m2lZPT3HjmzSzTsIRq2xmIpY2XlvHn4OPeMuyzIP-sUs7E</recordid><startdate>20141125</startdate><enddate>20141125</enddate><creator>Geng, Qing</creator><creator>Fan, Tao</creator><creator>Zhang, Boyou</creator><creator>Wang, Wei</creator><creator>Xu, Yao</creator><creator>Hu, Hao</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20141125</creationdate><title>Five microRNAs in plasma as novel biomarkers for screening of early-stage non-small cell lung cancer</title><author>Geng, Qing ; Fan, Tao ; Zhang, Boyou ; Wang, Wei ; Xu, Yao ; Hu, Hao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-74554a90c0b533259095acfffc1990d43a52dc0ae5a02ea9f382d76f31f81fe93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Accuracy</topic><topic>Analysis</topic><topic>Area Under Curve</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Carcinoma, Non-Small-Cell Lung - blood</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>Cell growth</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Comparative analysis</topic><topic>Diagnosis</topic><topic>Disease</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Genetic Testing - methods</topic><topic>Humans</topic><topic>Lung cancer</topic><topic>Lung cancer, Non-small cell</topic><topic>Lung Neoplasms - blood</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Materials selection</topic><topic>Medical imaging</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - blood</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Neoplasm Staging</topic><topic>Plasma</topic><topic>Predictive Value of Tests</topic><topic>Reproducibility of Results</topic><topic>Risk Factors</topic><topic>ROC Curve</topic><topic>Studies</topic><topic>Surgery</topic><topic>Thoracic surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geng, Qing</creatorcontrib><creatorcontrib>Fan, Tao</creatorcontrib><creatorcontrib>Zhang, Boyou</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Xu, Yao</creatorcontrib><creatorcontrib>Hu, Hao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest_Health &amp; 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In training set, 25 early-stage NSCLC patients and 25 matched healthy controls are included to assess the miRNA expression profile between early-stage NSCLC patients and healthy controls by real-time RT-PCR. We found that five of these miRNAs (miR-20a, miR-223, miR-21, miR-221 and miR-145) levels in NSCLC patients were significantly dysregulated compared with the healthy groups and thus were selected to validation set. Therefore, a validation experiment was further performed to investigate the potential predictive power of these five miRNAs based on 126 early-stage NSCLC patients, 42 NCPD patients and 60 healthy controls. The receiver operating characteristic (ROC) curves were generated for the five miRNAs. ROC curve analyses suggested that these five plasma miRNAs could be promising biomarkers for NSCLC, with relatively high AUC values as follows: miR-20a, 0.89 with 95% CI of [0.85-0.93]; miR-223, 0.94 with 95% CI of [0.91-0.96]; miR-21, 0.77 with 95% CI of [0.71-0.83]; miR-155, 0.92 with 95% CI of [0.89-0.96]; miR-145, 0.77 with 95% CI of [0.71-0.83]. Stratified analyses indicated that plasma miR-20a, miR-223, miR-21 and miR-145 showed better predictive value in smokers than in non-smokers, while miR-155 might be more suitable for non-smokers. In addition, all of these five miRNAs could differentiate NSCLC from controls with a higher accuracy in advanced stage and squamous carcinoma subgroups. In conclusion, our study suggested that five plasma miRNAs (miR-20a, miR-145, miR-21, miR-223 and miR-221) can be used as promising biomarkers in early screening of NSCLC. Nevertheless, further validation and optimizing improvement should be performed on larger sample to confirm our results.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>25421010</pmid><doi>10.1186/s12931-014-0149-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Accuracy
Analysis
Area Under Curve
Biological markers
Biomarkers
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Cancer
Carcinoma, Non-Small-Cell Lung - blood
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Care and treatment
Case-Control Studies
Cell growth
Chronic obstructive pulmonary disease
Comparative analysis
Diagnosis
Disease
Double-Blind Method
Female
Gene Expression Profiling - methods
Genetic Testing - methods
Humans
Lung cancer
Lung cancer, Non-small cell
Lung Neoplasms - blood
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Materials selection
Medical imaging
MicroRNA
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
Mortality
Neoplasm Staging
Plasma
Predictive Value of Tests
Reproducibility of Results
Risk Factors
ROC Curve
Studies
Surgery
Thoracic surgery
title Five microRNAs in plasma as novel biomarkers for screening of early-stage non-small cell lung cancer
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