Identification of potential differentially methylated gene-related biomarkers in endometriosis.

Aim: To identify epigenetic alterations of differentially expressed genes and screen out targeted therapeutic drugs in endometriosis. Methods: Based on the Gene Expression Omnibus database and a series of biological information analysis tools, supplemented by validation of clinical samples, aberrant DNA methylation-driven genes and their functions were explored, as well as possible targeted drugs. Results: This study screened out a range of DNA methylation-driven genes that were associated with powerful properties and corresponding pathways. Among them, BDNF and CCL2 were key genes in the development of endometriosis. Four chemical agents have been flagged as potential treatments for endometriosis. Conclusion: These candidate genes and small-molecule agents may be further explored as potential targets and drugs for endometriosis diagnosis and therapy, respectively.

[1]  Baoqing Zhang,et al.  Potential Targets and Action Mechanism of Gastrodin in the Treatment of Attention-Deficit/Hyperactivity Disorder: Bioinformatics and Network Pharmacology Analysis , 2022, Evidence-based complementary and alternative medicine : eCAM.

[2]  N. Stachenfeld,et al.  Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis. , 2022, Microvascular research.

[3]  H. Duan,et al.  BDNF and TrKB expression levels in patients with endometriosis and their associations with dysmenorrhoea , 2022, Journal of Ovarian Research.

[4]  Y. Zhu,et al.  SMYD2‐mediated TRAF2 methylation promotes the NF‐κB signaling pathways in inflammatory diseases , 2021, Clinical and translational medicine.

[5]  Yan Li,et al.  Identification of Key Differentially Methylated/Expressed Genes and Pathways for Ovarian Endometriosis by Bioinformatics Analysis , 2021, Reproductive Sciences.

[6]  A. Morris,et al.  Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis , 2021, Science Translational Medicine.

[7]  Hao Huang,et al.  A panel of differentially methylated regions enable prognosis prediction for colorectal cancer. , 2021, Genomics.

[8]  Qing Huan,et al.  LncRNA AFAP1‐AS1 regulates proliferation and apoptosis of endometriosis through activating STAT3/TGF‐β/Smad signaling via miR‐424‐5p , 2021, The journal of obstetrics and gynaecology research.

[9]  Zhenzhen Lu,et al.  Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis , 2021, Annals of medicine.

[10]  Ling Li,et al.  Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway , 2020, Frontiers in Endocrinology.

[11]  Jing Du,et al.  Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus , 2020, Journal of cellular and molecular medicine.

[12]  Yunfeng Fu,et al.  A novel epigenetic regulation of circFoxp1 on Foxp1 in colon cancer cells , 2020, Cell Death & Disease.

[13]  Shi Feng,et al.  Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway , 2020, Frontiers in Immunology.

[14]  Qing Yang,et al.  miR-96-5p regulated TGF-β/SMAD signaling pathway and suppressed endometrial cell viability and migration via targeting TGFBR1 , 2020, Cell cycle.

[15]  Feifei Hu,et al.  The inhibition of bone morphogenetic protein 1 attenuates endometriosis lesions in vivo and in vitro , 2020, Archives of Gynecology and Obstetrics.

[16]  E. Perdas,et al.  Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis , 2020, Journal of clinical medicine.

[17]  Jinhui Liu,et al.  Identification of aberrantly methylated differentially expressed genes and associated pathways in endometrial cancer using integrated bioinformatic analysis , 2020, Cancer medicine.

[18]  M. Bilotas,et al.  PI3K/AKT pathway is altered in the endometriosis patient’s endometrium and presents differences according to severity stage , 2020, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[19]  I. Shih,et al.  The Origin and Pathogenesis of Endometriosis. , 2020, Annual review of pathology.

[20]  L. Giudice,et al.  The endometrial immune environment of women with endometriosis. , 2019, Human reproduction update.

[21]  A. Masoudi-Nejad,et al.  Genome-wide DNA methylation profiling in ectopic and eutopic of endometrial tissues , 2019, Journal of Assisted Reproduction and Genetics.

[22]  C. Zeng,et al.  Farnesoid X Receptor Agonist GW4064 Inhibits Aromatase and ERβ Expression in Human Endometriotic Stromal Cells , 2018, Reproductive Sciences.

[23]  Robert N. Taylor,et al.  Curcumin attenuates proangiogenic and proinflammatory factors in human eutopic endometrial stromal cells through the NF‐κB signaling pathway , 2018, Journal of cellular physiology.

[24]  C. Tomassetti,et al.  Endometriosis and infertility: Insights into the causal link and management strategies. , 2018, Best practice & research. Clinical obstetrics & gynaecology.

[25]  K. Zondervan,et al.  Challenges in endometriosis miRNA studies - From tissue heterogeneity to disease specific miRNAs. , 2017, Biochimica et biophysica acta. Molecular basis of disease.

[26]  Yuan Yuan,et al.  Aberrantly methylated-differentially expressed genes and pathways in colorectal cancer , 2017, Cancer Cell International.

[27]  S. M. Kolk,et al.  MicroRNA-338 Attenuates Cortical Neuronal Outgrowth by Modulating the Expression of Axon Guidance Genes , 2016, Molecular Neurobiology.

[28]  Z. Chang,et al.  Correlations between gastric cancer family history and ROBO2 and RASSF2A gene methylations. , 2016, Journal of cancer research and therapeutics.

[29]  Damian Szklarczyk,et al.  STITCH 5: augmenting protein–chemical interaction networks with tissue and affinity data , 2015, Nucleic Acids Res..

[30]  C. Demetriou,et al.  Biological embedding of early‐life exposures and disease risk in humans: a role for DNA methylation , 2015, European journal of clinical investigation.

[31]  Sung-Wan Kim,et al.  BDNF Promoter Methylation Associated with Suicidal Ideation in Patients with Breast Cancer* , 2015, International journal of psychiatry in medicine.

[32]  W. Guo,et al.  Aberrant methylation and decreased expression of the TGF‐β/Smad target gene FBXO32 in esophageal squamous cell carcinoma , 2014, Cancer.

[33]  M. Butler,et al.  Over-expression of the miRNA cluster at chromosome 14q32 in the alcoholic brain correlates with suppression of predicted target mRNA required for oligodendrocyte proliferation. , 2013, Gene.

[34]  L. Giudice,et al.  Pathogenesis and pathophysiology of endometriosis. , 2012, Fertility and sterility.

[35]  Robert N. Taylor,et al.  Proteomic identification of neurotrophins in the eutopic endometrium of women with endometriosis. , 2012, Fertility and sterility.

[36]  J. Mei,et al.  Chemokine CCL2 enhances survival and invasiveness of endometrial stromal cells in an autocrine manner by activating Akt and MAPK/Erk1/2 signal pathway. , 2012, Fertility and sterility.

[37]  Y. Tsukamoto,et al.  Aberrant DNA methylation status of endometriosis: Epigenetics as the pathogenesis, biomarker and therapeutic target , 2011, The journal of obstetrics and gynaecology research.

[38]  K. Osteen,et al.  Development and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis. , 2011, Fertility and sterility.

[39]  Daniel E. Deatherage,et al.  Promoter hypermethylation of FBXO32, a novel TGF-β/SMAD4 target gene and tumor suppressor, is associated with poor prognosis in human ovarian cancer , 2010, Laboratory Investigation.

[40]  M. Widschwendter,et al.  Emerging promise of epigenetics and DNA methylation for the diagnosis and management of women's cancers. , 2010, Epigenomics.

[41]  N. Terakawa,et al.  Peroxisome proliferator-activated receptor-γ ligand reduced tumor necrosis factor-α-induced interleukin-8 production and growth in endometriotic stromal cells , 2008 .

[42]  Y. Kitaoka,et al.  Usefulness and limits of CA-125 in diagnosis of endometriosis without associated ovarian endometriomas. , 2005, Human reproduction.

[43]  U. Kayisli,et al.  Extracellular Matrix-Dependent Regulation of Fas Ligand Expression in Human Endometrial Stromal Cells , 2002, Biology of reproduction.

[44]  C. Plass,et al.  Methylation matters , 2001, Journal of medical genetics.

[45]  G. Dunselman,et al.  Adhesion of menstrual endometrium to extracellular matrix: the possible role of integrin α6β1 and laminin interaction , 2000 .