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Conference Paper: Expression profiling in lung adenocarcinomas with or without epidermal growth factor receptor (EGFR) gene mutation at exons 18 - 21 reveals expression signatures related to the EGFR pathway

TitleExpression profiling in lung adenocarcinomas with or without epidermal growth factor receptor (EGFR) gene mutation at exons 18 - 21 reveals expression signatures related to the EGFR pathway
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research
Citation
The 96th Annual Meeting of the American Association for Cancer Research (AACR 2005), Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9 suppl., p. 207-208 abstract no. 883 How to Cite?
AbstractBackground: Lung cancer is a leading cause of cancer morbidity and mortality worldwide related to advanced staging at the time of presentation or diagnosis. Epidermal Growth Factor Receptor (EGFR) with activating mutations is a potential new molecular therapeutic target responsive to tyrosine kinase inhibitor therapy. Our hypothesis is that there are differential expression gene signatures between lung adenocarcinomas with or without EGFR mutation Methods: Total RNA from 49 resected primary lung adenocarcinomas were analyzed individually for their expression profiles by Affymetrix GeneChip HG-U133 set according to standard protocols. EGFR mutations at exons 18-21 were evaluated by sequencing of cDNA. Expression data were analyzed with publicly available software packages for microarray analysis. Results: 29 tumors showed EGFR mutations (23/32 women, 6/17 men). The mutant cases were significantly associated with life time never smokers (26/32) compared to current or previous smokers. After data normalization across all cases and exclusion of genes showing significant proportion of absent call and genes showing low variance, differential gene expression was compared between tumors with or without EGFR mutations using log transformed signal intensities and two sample t-tests, yielding 318 genes that showed significantly (p<=0.01) higher or lower expression by two fold difference between groups. Hierarchical clustering aiming at detection of co-regulated or co-expressed genes showed significant sample clustering including groups that contained predominantly tumors with or without EGFR mutation. Molecular classification was done with Support Vector Machine with Leave-one out analysis and the Machine Learning Performance was 96% sensitivity and 80% specificity in the prediction of tumours with EGFR mutation. Some examples of differentially expressed genes and molecular classifiers included EGFR, FGFR3, EREG, WIF3, INHBA and TNFSF10. Conclusion: We have identified differentially-expressed and class-predictive genes in primary lung adenocarcinomas with respect to EGFR gene mutation status at exons 18-21. These genes are potentially involved in the EGFR oncogenic pathway and serve as putative diagnostic or therapeutic targets in the management of lung cancer. (Supported by HKSAR RGC grants 7310/01M, 7486/03M, 7468/04M)
Persistent Identifierhttp://hdl.handle.net/10722/104412
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorLam, DCLen_HK
dc.contributor.authorWong, MPen_HK
dc.contributor.authorGirard, Len_HK
dc.contributor.authorShigematsu, Hen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorGazdar, AFen_HK
dc.contributor.authorChiu, SWen_HK
dc.contributor.authorSuen, WSen_HK
dc.contributor.authorLam, WKen_HK
dc.contributor.authorMinna, JDen_HK
dc.date.accessioned2010-09-25T21:52:01Z-
dc.date.available2010-09-25T21:52:01Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 96th Annual Meeting of the American Association for Cancer Research (AACR 2005), Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9 suppl., p. 207-208 abstract no. 883en_HK
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104412-
dc.description.abstractBackground: Lung cancer is a leading cause of cancer morbidity and mortality worldwide related to advanced staging at the time of presentation or diagnosis. Epidermal Growth Factor Receptor (EGFR) with activating mutations is a potential new molecular therapeutic target responsive to tyrosine kinase inhibitor therapy. Our hypothesis is that there are differential expression gene signatures between lung adenocarcinomas with or without EGFR mutation Methods: Total RNA from 49 resected primary lung adenocarcinomas were analyzed individually for their expression profiles by Affymetrix GeneChip HG-U133 set according to standard protocols. EGFR mutations at exons 18-21 were evaluated by sequencing of cDNA. Expression data were analyzed with publicly available software packages for microarray analysis. Results: 29 tumors showed EGFR mutations (23/32 women, 6/17 men). The mutant cases were significantly associated with life time never smokers (26/32) compared to current or previous smokers. After data normalization across all cases and exclusion of genes showing significant proportion of absent call and genes showing low variance, differential gene expression was compared between tumors with or without EGFR mutations using log transformed signal intensities and two sample t-tests, yielding 318 genes that showed significantly (p<=0.01) higher or lower expression by two fold difference between groups. Hierarchical clustering aiming at detection of co-regulated or co-expressed genes showed significant sample clustering including groups that contained predominantly tumors with or without EGFR mutation. Molecular classification was done with Support Vector Machine with Leave-one out analysis and the Machine Learning Performance was 96% sensitivity and 80% specificity in the prediction of tumours with EGFR mutation. Some examples of differentially expressed genes and molecular classifiers included EGFR, FGFR3, EREG, WIF3, INHBA and TNFSF10. Conclusion: We have identified differentially-expressed and class-predictive genes in primary lung adenocarcinomas with respect to EGFR gene mutation status at exons 18-21. These genes are potentially involved in the EGFR oncogenic pathway and serve as putative diagnostic or therapeutic targets in the management of lung cancer. (Supported by HKSAR RGC grants 7310/01M, 7486/03M, 7468/04M)-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titleExpression profiling in lung adenocarcinomas with or without epidermal growth factor receptor (EGFR) gene mutation at exons 18 - 21 reveals expression signatures related to the EGFR pathwayen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailWong, MP: mwpik@hkucc.hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.emailLam, WK: lamwk@hku.hken_HK
dc.identifier.authorityWong, MP=rp00348en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.hkuros101785en_HK
dc.identifier.volume65en_HK
dc.identifier.issue9 suppl.-
dc.identifier.spage207, abstract no. 883-
dc.identifier.epage208-

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