A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas
The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade glio...
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| Veröffentlicht in: | Oncology reports 2017-01, Vol.37 (1), p.10-22 |
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| creator | Ponnampalam, Stephen N Kamaluddin, Nor Rizan Zakaria, Zubaidah Matheneswaran, Vickneswaran Ganesan, Dharmendra Haspani, Mohammed Saffari Ryten, Mina Hardy, John A |
| description | The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p |
| doi_str_mv | 10.3892/or.2016.5285 |
| format | Article |
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In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (p<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2016.5285</identifier><identifier>PMID: 28004117</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Adult ; Age ; Aged ; Blood ; Blood-brain barrier ; Brain cancer ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Care and treatment ; Cellular signal transduction ; Chronic fatigue syndrome ; Consent ; Development and progression ; Disease ; Female ; Gender ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Glioma ; Glioma - blood ; Glioma - genetics ; Glioma - pathology ; Gliomas ; Growth factors ; Health aspects ; Histopathology ; Homeostasis ; Humans ; Kinases ; Male ; Medical prognosis ; Medical screening ; Middle Aged ; Nervous system ; NMR ; Nuclear magnetic resonance ; Oligonucleotide Array Sequence Analysis - methods ; Patients ; Polymerase Chain Reaction - methods ; Principal Component Analysis ; Proteins ; Reproducibility of Results ; Signal Transduction - genetics ; Stroke ; Surgery ; Transcriptome ; Tumor necrosis factor-TNF ; Tumors</subject><ispartof>Oncology reports, 2017-01, Vol.37 (1), p.10-22</ispartof><rights>COPYRIGHT 2017 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><rights>Copyright: © Ponnampalam et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-41d36cfe7facd1ddf83f29276bb10c83fb446bb5572582965460f7dcb654c64e3</citedby><cites>FETCH-LOGICAL-c510t-41d36cfe7facd1ddf83f29276bb10c83fb446bb5572582965460f7dcb654c64e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28004117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ponnampalam, Stephen N</creatorcontrib><creatorcontrib>Kamaluddin, Nor Rizan</creatorcontrib><creatorcontrib>Zakaria, Zubaidah</creatorcontrib><creatorcontrib>Matheneswaran, Vickneswaran</creatorcontrib><creatorcontrib>Ganesan, Dharmendra</creatorcontrib><creatorcontrib>Haspani, Mohammed Saffari</creatorcontrib><creatorcontrib>Ryten, Mina</creatorcontrib><creatorcontrib>Hardy, John A</creatorcontrib><title>A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (p<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.</description><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Blood</subject><subject>Blood-brain barrier</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Care and treatment</subject><subject>Cellular signal transduction</subject><subject>Chronic fatigue syndrome</subject><subject>Consent</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Female</subject><subject>Gender</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Glioma</subject><subject>Glioma - blood</subject><subject>Glioma - genetics</subject><subject>Glioma - pathology</subject><subject>Gliomas</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Histopathology</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Kinases</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical screening</subject><subject>Middle Aged</subject><subject>Nervous system</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Patients</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Principal Component Analysis</subject><subject>Proteins</subject><subject>Reproducibility of Results</subject><subject>Signal Transduction - genetics</subject><subject>Stroke</subject><subject>Surgery</subject><subject>Transcriptome</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumors</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptksuLFDEQxhtR3IfePEtAkD3YYx6ddPdFGBZfsOBFwVtIJ5XuLJlkTLod5783467LjEgOqar86kuofFX1guAV63r6NqYVxUSsOO34o-qctD2pacPI4xJjSmrG-Pez6iLnW4xpi0X_tDqjHcYNIe15tV2jwcdo6kFlMGiEAAh-bRPk7GJAKhiU3RiUd2FEWzVPO7UvVeX32WU0R2SctZAgzE7NgAaYdwABTW6c_jT7uENjUgbQ6F3cqPysemKVz_D8fr-svn14__X6U33z5ePn6_VNrTnBc90Qw4S20FqlDTHGdszSnrZiGAjWJRmapsSct5R3tBe8Edi2Rg8l0qIBdlm9u9PdLsMGjC4vTMrLbXIblfYyKidPT4Kb5Bh_Ss44F0IUgat7gRR_LJBnuXFZg_cqQFyyJB0noue8wwV99Q96G5dUhlSontGOiI4dUaPyIF2wsdyrD6Jy3bR9SzgWpFCr_1BlGdg4HQNYV-onDa-PGiZQfp5y9Mtc_i-fgm_uQJ1izgnswzAIlgcryZjkwUryYKWCvzwe4AP81zvsNzSRw-k</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Ponnampalam, Stephen N</creator><creator>Kamaluddin, Nor Rizan</creator><creator>Zakaria, Zubaidah</creator><creator>Matheneswaran, Vickneswaran</creator><creator>Ganesan, Dharmendra</creator><creator>Haspani, Mohammed Saffari</creator><creator>Ryten, Mina</creator><creator>Hardy, John A</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. 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genetics</topic><topic>Brain Neoplasms - pathology</topic><topic>Care and treatment</topic><topic>Cellular signal transduction</topic><topic>Chronic fatigue syndrome</topic><topic>Consent</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Female</topic><topic>Gender</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Glioma</topic><topic>Glioma - blood</topic><topic>Glioma - genetics</topic><topic>Glioma - pathology</topic><topic>Gliomas</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Histopathology</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Kinases</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical screening</topic><topic>Middle Aged</topic><topic>Nervous system</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Oligonucleotide Array Sequence Analysis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ponnampalam, Stephen N</au><au>Kamaluddin, Nor Rizan</au><au>Zakaria, Zubaidah</au><au>Matheneswaran, Vickneswaran</au><au>Ganesan, Dharmendra</au><au>Haspani, Mohammed Saffari</au><au>Ryten, Mina</au><au>Hardy, John A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>37</volume><issue>1</issue><spage>10</spage><epage>22</epage><pages>10-22</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (p<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>28004117</pmid><doi>10.3892/or.2016.5285</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology reports, 2017-01, Vol.37 (1), p.10-22 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Age Aged Blood Blood-brain barrier Brain cancer Brain Neoplasms - genetics Brain Neoplasms - pathology Care and treatment Cellular signal transduction Chronic fatigue syndrome Consent Development and progression Disease Female Gender Gene expression Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic Genetic aspects Glioma Glioma - blood Glioma - genetics Glioma - pathology Gliomas Growth factors Health aspects Histopathology Homeostasis Humans Kinases Male Medical prognosis Medical screening Middle Aged Nervous system NMR Nuclear magnetic resonance Oligonucleotide Array Sequence Analysis - methods Patients Polymerase Chain Reaction - methods Principal Component Analysis Proteins Reproducibility of Results Signal Transduction - genetics Stroke Surgery Transcriptome Tumor necrosis factor-TNF Tumors |
| title | A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas |
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