Background:
Endometriosis is a complex gynecologic disorderthat affects as many as ۱۰-۱۵% of premenopausal women.The pathogenesis of endometriosis, as the presence of endometrium-like tissue outside the uterine cavity, is largely unknown.The purpose of this study is to identify causative genes in thisdisease with focus on HOX family genes and their regulatinggenes. HOX genes, encoding homeodomain transcription factors,are dynamically expressed in endometrium, where they arenecessary for endometrial growth, differentiation, and implantation.Network theory allows for a holistic understanding ofthe role of genes in diseases.Materials and Methods: PCR array data of ۸۴ candidate genesused to construct co-expression network based on pearson'scorrelation. The study performed on ۱۵ ectopic, ۱۵ eutopic and۱۵ normal tissues. Five tissues in each ectopic, eutopic and normalgroup were pooled as three biological repeats.Results: Comparison of gene expression patterns betweenectopic and eutopic with normal samples, revealed that theexpression of ۳۳ and ۴۴ genes has significantly changed in eutopicand ectopic samples, respectively. Twenty two of geneswere shared between two groups. The five genes of ISL۲,HOXC۱۲, LBX۱, HOXC۱۳ and EN۱ exhibited the highestsignificant up-regulation (P≤۰.۰۰۸) in eutopic vs. normal samples.ISL۲ was not involved in any network. HOXC۱۲ was ahub in a network. Some of its connections have been changedin eutopic samples. The node degree of LBX۱ and EN۱ wasfive and it involved in a network, which has not seen in theeutopic samples. HOXC۱۳ was a hub in a network which hasnot seen in eutopic samples. The five genes MKX, DLX۶,HOXB۸, MSX۲ and ARX exhibited the highest significance(P≤۰.۰۰۰۲) in the ectopic vs. normal samples. MKX and ARXwere down-regulated and three other genes were up-regulated.MKX was a hub in a network which has not seen in ectopicsamples. The node degree of DLX۶ was four in normal sampleswhereas in the ectopic samples its connections have beenchanged. HOXB۸ was not involved in any network in controlsamples while in the ectopic samples it belongs to a networkand its degree was five. ARX and MSX۲ belong to a networkin normal samples but in the ectopic samples, MSX۲ belongsto a large network and its degree was twelve while, ARX wasnot owned by any network in ectopic samples. ISL۲ and EN۱play role in neurogenesis, MSX۲ plays role in the apoptosis ofneural crest. HOXC۱۲, HOXC۱۳, MKX, DLX۶, HOXB۸ andARX play role in development and LBX۱ plays role in theformation of muscle.Conclusion: In the study, the most differentially expressedgenes of patient vs. normal samples are effective genes in development.The study of co-expression networks between candidategenes showed that all of these genes, with the exceptionof HOXB۸, have many interactions with the other genesstudied, which are characteristic of developmental genes. Thesefindings indicated correlation between developmental genes information of eutopic and ectopic endometrium cell.