Abstract
BackgroundEndometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis.MethodsWe applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets.ResultsWe find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues.ConclusionThe study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.
Highlights
IntroductionGene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis
Reproductive Biology and Endocrinology 2009, 7:94 http://www.rbej.com/content/7/1/94 anisms involved in endometriosis are still uncovered, the classification of this disease evolved from a local disorder to a complex, chronic systemic disease [3]
Data were included in our re-analysis if they met the following conditions: 1) the data is in genomewide; 2) comparison was conducted between endometriosis patients and controls; 3) complete microarray raw or normalized data are available
Summary
Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Reproductive Biology and Endocrinology 2009, 7:94 http://www.rbej.com/content/7/1/94 anisms involved in endometriosis are still uncovered, the classification of this disease evolved from a local disorder to a complex, chronic systemic disease [3]. Gene expression profiling has been used in several studies of endometriosis, in which from a few to hundreds differentially expressed genes were identified [4,5,6,7,8,9,10,11,12,13,14,15,16,17]. It is hard to interpret individual genes on a list with many significant genes
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