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Series GSE4888

Query DataSets for GSE4888

Status

Public on May 24, 2006

Title

Molecular phenotyping of human endometrium

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

To examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole genome molecular phenotyping (54,600 genes/ESTs) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. The results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and 4 including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.
Keywords: Gene expression arrays human endometrium

Overall design

Unsupervised principal component analysis (PCA) of all samples revealed that samples selfcluster into four groups consistent with histologic phenotypes of proliferative (PE), early secretory (ESE), mid-secretory (MSE), and late secretory (LSE) endometrium. Independent hierarchical clustering analysis revealed equivalent results, with 2 major dendrogram branches corresponding to PE/ESE and MSE/LSE and sub-branching into the 4 respective phases with heterogeneity among samples within each sub-branch. K-means clustering of genes revealed 4 major patterns of gene expression (high in PE, high in ESE, high in MSE, and high in LSE), and gene ontology analysis of these clusters demonstrated cycle-phase specific biological processes and molecular functions. Six samples with ambiguous histology were identically assignable to a cycle phase by both PCA and hierarchical clustering. Additionally, pair-wise comparisons of relative gene expression across the cycle revealed genes/families that clearly distinguish the transitions of PE to ESE, ESE to MSE, and MSE to LSE, including receptomes and signaling pathways. Select genes were validated by quantitative RT-PCR.

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