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Expression profiling identifies genes involved in emphysema severity.

Francis SM, Larsen JE, Pavey SJ, Bowman RV, Hayward NK, Fong KM, Yang IA - Respir. Res. (2009)

Bottom Line: Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes.Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01).Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia. ss.francis@uqconnect.edu.au

ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients.Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.

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Comparison of mRNA expression in seven candidate genes between TPCH test (n = 30, microarray) and training set (n = 62 qRT-PCR data), with two public microarray datasets of lung tissue samples (Spira et al, [12], n = 34; and Golpon et al [13], n = 10). Fold change represents mean expression ratio of moderate versus mild emphysema (TPCH training set), severe/mild emphysema versus normal (Spira et al), or severe emphysema versus normal samples (Golpon et al). The absence of a bar indicates the gene was not represented on the microarray platform.
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Figure 3: Comparison of mRNA expression in seven candidate genes between TPCH test (n = 30, microarray) and training set (n = 62 qRT-PCR data), with two public microarray datasets of lung tissue samples (Spira et al, [12], n = 34; and Golpon et al [13], n = 10). Fold change represents mean expression ratio of moderate versus mild emphysema (TPCH training set), severe/mild emphysema versus normal (Spira et al), or severe emphysema versus normal samples (Golpon et al). The absence of a bar indicates the gene was not represented on the microarray platform.

Mentions: These 11 genes were submitted to biological replication in a test set of 62 lung samples from the TPCH lung tissue bank. Of the 11 genes selected from microarray analysis and technically validated by qRT-PCR, eight displayed concordant increased or decreased expression. Seven of the genes displayed greater than 1.3 fold changes in expression between moderate versus mild emphysema lung samples in the TPCH test set. These seven candidate emphysema severity genes were 60% (59% sensitive and 62% specific) accurate in classifying mild and moderate emphysema patients in TPCH independent test, 83% (83% sensitive and 83% specific) and 80% (80% sensitive and 80% specific) accurate in classifying normal and severe emphysema patients in Spira and Golpon studies respectively (See Additional file 5). The qRT-PCR expression results of the training and independent test sets are shown in Figure 2a &2b. In silico comparison of direction of gene expression between the three studies displayed five of seven genes to be concordant between Spira and TPCH cohort. Three of the five genes common with the HuGeneFL platform were observed to be concordant in direction of expression between the Golpon and TPCH cohorts (Figure 3).


Expression profiling identifies genes involved in emphysema severity.

Francis SM, Larsen JE, Pavey SJ, Bowman RV, Hayward NK, Fong KM, Yang IA - Respir. Res. (2009)

Comparison of mRNA expression in seven candidate genes between TPCH test (n = 30, microarray) and training set (n = 62 qRT-PCR data), with two public microarray datasets of lung tissue samples (Spira et al, [12], n = 34; and Golpon et al [13], n = 10). Fold change represents mean expression ratio of moderate versus mild emphysema (TPCH training set), severe/mild emphysema versus normal (Spira et al), or severe emphysema versus normal samples (Golpon et al). The absence of a bar indicates the gene was not represented on the microarray platform.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2746189&req=5

Figure 3: Comparison of mRNA expression in seven candidate genes between TPCH test (n = 30, microarray) and training set (n = 62 qRT-PCR data), with two public microarray datasets of lung tissue samples (Spira et al, [12], n = 34; and Golpon et al [13], n = 10). Fold change represents mean expression ratio of moderate versus mild emphysema (TPCH training set), severe/mild emphysema versus normal (Spira et al), or severe emphysema versus normal samples (Golpon et al). The absence of a bar indicates the gene was not represented on the microarray platform.
Mentions: These 11 genes were submitted to biological replication in a test set of 62 lung samples from the TPCH lung tissue bank. Of the 11 genes selected from microarray analysis and technically validated by qRT-PCR, eight displayed concordant increased or decreased expression. Seven of the genes displayed greater than 1.3 fold changes in expression between moderate versus mild emphysema lung samples in the TPCH test set. These seven candidate emphysema severity genes were 60% (59% sensitive and 62% specific) accurate in classifying mild and moderate emphysema patients in TPCH independent test, 83% (83% sensitive and 83% specific) and 80% (80% sensitive and 80% specific) accurate in classifying normal and severe emphysema patients in Spira and Golpon studies respectively (See Additional file 5). The qRT-PCR expression results of the training and independent test sets are shown in Figure 2a &2b. In silico comparison of direction of gene expression between the three studies displayed five of seven genes to be concordant between Spira and TPCH cohort. Three of the five genes common with the HuGeneFL platform were observed to be concordant in direction of expression between the Golpon and TPCH cohorts (Figure 3).

Bottom Line: Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes.Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01).Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia. ss.francis@uqconnect.edu.au

ABSTRACT
Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients.Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.

Show MeSH
Related in: MedlinePlus