Endometriosis Gene Expression Heterogeneity and Biosignature: A Phylogenetic Analysis

Abstract

Endometriosis is a multifactorial disease with poorly understood etiology, and reflecting an evolutionary nature where genetic alterations accumulate throughout pathogenesis. Our objective was to characterize the heterogeneous pathological process using parsimony phylogenetics. Gene expression microarray data of ovarian endometriosis obtained from NCBI database were polarized and coded into derived (abnormal) and ancestral (normal) states. Such alterations are referred to as synapomorphies in a phylogenetic sense (or biomarkers). Subsequent gene linkage was modeled by Genomatix BiblioSphere Pathway software. A list of clonally shared derived (abnormal) expressions revealed the pattern of heterogeneity among specimens. In addition, it has identified disruptions within the major regulatory pathways including those involved in cell proliferation, steroidogenesis, angiogenesis, cytoskeletal organization and integrity, and tumorigenesis, as well as cell adhesion and migration. Furthermore, the analysis supported the potential central involvement of ESR2 in the initiation of endometriosis. The pathogenesis mapping showed that eutopic and ectopic lesions have different molecular biosignatures.

The role of tissue factor and protease‐activated receptor 2 in endometriosis

“…This showed the potential pathologic roles of eutopic endometrium in endometriosis . The differential gene expressions are probably dedicated to primary disorders residing in the eutopic endometrium, which suggests that this novel signal, TF/PAR‐2 may be involved in the initial phase of endometriosis.…”

“…The co‐upregulated expression of TF and PAR‐2 in secretory phase in eutopic endometrium seems to plan the next menstrual cycle, potentially predisposing to survival and implantation of retrograde menstruated endometrial cells in the abdominal cavity . This showed the potential pathologic roles of eutopic endometrium in endometriosis . The differential gene expressions are probably dedicated to primary disorders residing in the eutopic endometrium, which suggests that this novel signal, TF/PAR‐2 may be involved in the initial phase of endometriosis.…”

“…Currently, the role of eutopic endometrium in patients with endometriosis has been noted by scholars because this tissue seems to play a central role in the physiopathology of the disease. Both the differential gene transcription expression of eutopic endometrium with endometriosis and the respondence of eutopic endometrium to sex hormones are important clues for evaluating the pathologic role of eutopic endometrium in the disease.…”

Gonadotropin‐releasing hormone agonist induces downregulation of tensin 1 in women with endometriosis

“…In the gynecologic system, TNS1 is involved in implantation and oogenesis, and is expressed in the endometrium . A phylogenetic study of ovarian endometriosis revealed that TNS1 is overexpressed in endometriotic tissue compared with eutopic tissues . However, no reports to date have described the effect of hormonal treatment on TNS1 expression in women with endometriosis.…”

The scar constituent Collagen I triggers coordinated collective migration and invasion in a 3D spheroid model of early endometriotic lesions

“…Unfortunately, these treatments are not curative and have high associated side effects and remission rates 1,2 . While targeted therapies are urgently needed, their development has been hindered by the heterogeneity 3,4 and limited mechanistic understanding of the disease. Based on the widely accepted Sampson's theory, endometriosis arises when tissue fragments shed during menstruation implant in the surrounding tissue 5 .…”