Network-based bioinformatics analysis of HOX genes and their related genes in endometriosis

Abstract

Background: Dysregulation of some HOX genes are important for the development of endometriosis. Endometriosis is a complex gynecologic disorder affecting as many as 10-15% of premenopausal women. The pathogenesis of endometriosis, as the presence of endometrium-like tissue outside the uterine cavity, is largely unknown. HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, in which they are necessary for endometrial growth, differentiation, and implantation. Few investigations have been studied in this vast range of HOX genes with a network-based view. Network theory allows for a holistic understanding of the role of genes in diseases. The purpose of this study is to identify genes that cause this disease by focusing on the HOX family genes and their regulatory genes. Materials & Methods: Fifteen samples of eutopic and ectopic endometrium collected from patients in proliferation phase. PCR array was performed on sample groups for 84 HOX genes and their related genes. The statistical significance was determined by using t-test. PCA and Hierarchical clustering were carried out between different groups. The genes co-expression networks were constructed based on correlation between normalized gene expression data. Gene function was annotated based on Gene Ontology, the intervention in other diseases and expression in other tissues using the DAVID to clarify the function of important genes and the mechanism of endometriosis. Results: Among the analyzed genes, 30, 40 and 35 significantly differentially expressed genes were in eutopic, ectopic compared with normal and ectopic with eutopic samples, respectively. Twenty-eight genes had no significant alteration in none of the sample groups. Conclusion: The most significant genes and the genes in co-expression networks are effective genes in development, metabolic and neural processes. Another important point is that the some non-differently expressed genes in networks have many interactions with the significant genes, indicating that these non-significant genes also are likely contributed in endometriosis. Keywords: endometriosis, HOX, PCR-array, Co-expression network