مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
The Use of Biomarkers; A Promising Solution for Diagnosing Endometriosis
The Use of Biomarkers; A Promising Solution for Diagnosing Endometriosis
Solmaz Allahverdi Meygooni,1Maryam Shahhoseini,2Azam Dalman,3,*
1. 1. Faculty of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran/ 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 2. Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 3. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Introduction: Endometriosis (EM) is a common cause of infertility in women, characterized by an extended period between symptoms onset and diagnosis confirmation. A postponement in diagnosing EM can lead to delayed treatment or inadequate care, potentially increasing the risk of infertility and organ damage. Therefore, it is essential to identify the genes associated with EM to conduct timely diagnoses.
Methods: For this purpose, data were obtained from GSE7305, and then a protein-protein interaction network was drawn for genes with log2FC>1 and adj.P.Val <0.05. Based on the network obtained from the STRING database, Fibronectin 1 (FN1), C-C motif Chemokine Ligand 2 (CCL2), Intercellular Adhesion Molecule-1 (ICAM-1), Apolipoprotein (ApoE) and Chemokine C-X-C motif Ligand 8 (CXCL8) genes were recognized as high degree hub genes in EM.
Results: Furthermore, these genes demonstrated higher expression levels in EM compared to the control group in the GEO Profile. An analysis using the Enrichr database indicated that these genes are associated to the EM phenotype.
FN1 is a significant angiogenic factor that is essential for ovarian structure and processes such as migration, cell adhesion, growth, and differentiation. Increased FN1 expression correlates with increased cell proliferation indicating that the FN1 gene may play a role in the persistence of EM lesions. A meta-analysis of Single Nucleotide Polymorphisms (SNPs) has demonstrated the link between FN1 and moderate to severe cases of EM. In addition, it has been reported that FN1 expression is increased in EM patients. Various studies have also identified this gene as a potential biomarker for EM and several cancers, including stomach cancer, ovarian cancer, clear cell renal cell carcinoma, and breast cancer.
CCL2 has the potential to directly influence angiogenesis, which may play a role in the development of EM. Studies indicate that CCL2 serves as a valuable biomarker for prostate cancer and oral squamous cell carcinoma.
ICAM-1 is identified as a surface glycoprotein and can be a biomarker for breast cancer and systemic lupus erythematosus. This gene is involved in enhancing adhesion during immune and inflammatory responses and serves as a significant marker for oocyte quality and embryo development. Furthermore, studies suggest that genetic polymorphism in the ICAM-1 gene may influence susceptibility to EM. It has been shown that this gene exhibits high expression levels in endometrial tissues, thereby linking it to the progression of EM severity.
ApoE is a multifunctional protein that is a component of high-density lipoprotein and serves as a potential biomarker for various cancers, including papillary thyroid carcinoma, gastric cancer, and breast cancer. It is the primary source of cholesterol precursors necessary for the synthesis of ovarian estrogen and progesterone, suggesting its significant role in the initiation and progression of EM. Increased levels of APOE in women with EM can contribute to adhesion, endometrial attachment, or invasion thereby exacerbating lesion progression through a self-replicating mechanism. Consequently, increased ApoE levels may be associated with a reduced number of retrieved mature oocytes in older women and an increased risk of spontaneous pregnancy loss in patients suffering from EM.
CXCL8 is produced by various types of cells such as endometrial cells and mesothelial cells. studies indicate that it may serve as a biomarker for several cancers, including breast cancer, gastric cancer, and colorectal cancer. Additionally, CXCL8 plays a role in promoting angiogenesis, invasion, proliferation, and migration. A study revealed that elevated CXCL8 levels in follicular fluid and cumulus cells correlate with a decreased number of retrieved oocytes, MII oocytes, and the percentage of oocyte maturation. Furthermore, studies have demonstrated that the expression of CXCL8 in EM is higher than that in normal endometrial tissue; suggesting a potential involvement of this gene in the induction of EM.
Conclusion: The results suggest that FN1, CCL2, ICAM-1, APOE, and CXCL8 genes play a crucial role in the onset and progression of EM. Consequently, these genes may serve as promising non-invasive biomarkers for diagnosing EM. Further research could enhance our understanding of EM mechanisms and expand the diagnostic options available for women suffering from this condition, ultimately alleviating the economic and physical burdens associated with the disease.