HOXB4 Immunoreactivity in Endometrial Tissues From Women With or Without Endometriosis

Abstract

Endometriosis is a common disease characterized by the presence of ectopic endometrial tissue. Although the pathogenesis of endometriosis remains unclear, several factors have been implicated, including the dysregulation of homeobox ( HOX) genes. Our objective was to investigate the localization and immunoreactivity of HOXB4 in endometrial tissues from women with or without endometriosis. We studied samples of eutopic endometrium (EE), endometriomas (Eoma), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE) from 34 women with endometriosis, as well as eutopic endometrium from 38 women without endometriosis (EC). HOXB4 localization and immunoreactivity was assessed using immunohistochemistry and histoscore analysis. Data were analyzed with and without stratification by menstrual cycle phase. HOXB4 protein was present in the nuclei of endometrial glandular epithelial cells but not in stromal cells. HOXB4 immunoreactivity was reduced in DIE samples compared to all other groups. A smaller reduction in HOXB4 immunoreactivity was observed in SE samples compared to EC samples. HOXB4 immunoreactivity was significantly greater in proliferative compared to secretory phase samples in the EC group but not in EE, Eoma, or DIE groups. Among only proliferative phase samples, HOXB4 immunoreactivity was reduced in EE, Eoma, and DIE groups compared to EC. Based on these data, we suggest that an impaired capacity of eutopic and ectopic endometrial tissue to upregulate levels of HOXB4 during the proliferative phase may play a role in the pathogenesis of endometriosis and that further downregulation of HOXB4 may enhance ectopic implant invasiveness.

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

“…HOXB2, B3, B4, B7 and B9 genes which we observed their upregulation in association with endometriosis, was previously shown that are in contribution with endometriosis, and also are involved in progression and development of many cancers [27,[31][32][33][34][35][36][37][38][39]. About HOXC6, C8, C9, C10, C11, C12 and C13 genes which were analyzed here, no other studies have paid attention to the relationship between these genes and endometriosis, although their involvement with female reproductive tract are vastly shown [29].…”

“…The importance of HOXB genes in endometriosis were also pointed out [27]. In the current survey, five genes out of 7 genes of HOXB cluster were of DEGs in the eutopic, ectopic or both of them and most of them upregulated (Fig.…”

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

“…The importance of HOXB genes in endometriosis were also pointed out [26]. In the current survey, five genes out of 7 genes of HOXB cluster were of DEGs in the eutopic, ectopic or both of them and most of them upregulated (Fig.…”

“…The pathogenesis of endometriosis which was related to infertility remains unclear, but studies have shown that dysregulation HOX genes are important for the development of endometriosis [2,[26][27][28].…”

Uncovering Potential Roles of Differentially Expressed Genes, Upstream Regulators, and Canonical Pathways in Endometriosis Using an In Silico Genomics Approach

“…Alteration in expression of HOXB4 [42], apelin peptide [43], interleukin 18 [44], estrogen and progesterone receptors [45], integrin β3 and osteopontin (OPN) [46], microRNA-29c, and FKBP4 [47] have been reported. Varied expression levels of metastasis-inducing proteins (S100P, S100A4, OPN, and anterior gradient homologue 2 (AGR2)) have been shown to enhance pathogenesis by increasing endometrial cell invasiveness and establishing endometriotic ectopic deposits after retrograde menstruation [48].…”