Omics-based novel strategies in the diagnosis of endometriosis

Samare-Najaf, Mohammad; Razavinasab, Seyed Ali; Samareh, Ali; Jamali, Navid

doi:10.1080/10408363.2023.2270736

Cited by 3 publications

(2 citation statements)

References 215 publications

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“…Recent technological advances have significantly enhanced the assessment of genome-wide gene activity. Current research aims to identify biomarkers and elucidate pathogenic mechanisms [ 8 , 9 ]. Various specimens, including endometrial tissues [ 10 , 11 ], blood [ 12 ], urine [ 13 ], peritoneal fluid [ 14 ], and follicular fluid [ 15 ], have undergone diverse omics analyses, providing valuable but predominantly single-omics-focused insights.…”

Section: Introductionmentioning

confidence: 99%

Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis

Yang,

Jiang,

Ding

et al. 2024

J Transl Med

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Background Endometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear. Methods We employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson’s correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins. Results Integration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further multi-omics integration highlighted the essential role of ubiquitination in key fibrosis regulators in endometriosis. Correlation analysis between proteome and ubiquitylome showed correlation coefficients of 0.32 and 0.36 for ubiquitinated fibrosis proteins in EC/NC and EC/EU groups, respectively, indicating positive regulation of fibrosis-related protein expression by ubiquitination in ectopic lesions. We identified ubiquitination in 41 pivotal proteins within the fibrosis-related pathway of endometriosis. Finally, the elevated expression of TGFBR1/α-SMA/FAP/FN1/Collagen1 proteins in EC tissues were validated across independent samples. More importantly, we demonstrated that both the mRNA and protein levels of TRIM33 were reduced in endometriotic tissues. Knockdown of TRIM33 promoted TGFBR1/p-SMAD2/α-SMA/FN1 protein expressions in hESCs but did not significantly affect Collagen1/FAP levels, suggesting its inhibitory effect on fibrosis in vitro. Conclusions This study, employing multi-omics approaches, provides novel insights into endometriosis ubiquitination profiles and reveals aberrant expression of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, emphasizing their critical involvement in fibrosis pathogenesis and potential therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis

Yang,

Jiang,

Ding

et al. 2024

J Transl Med

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“…Additionally, alterations in the metabolomic profiles of tissue and fluid (blood, follicular fluid) occur in cases of endometriosis [16][17][18][19] with lipids playing a significant role in these profile changes [19]. Mass spectrometry analysis methods, coupled with chromatography or direct analysis (SELDI-, MALDI, shotgun), are effective for metabolic profiling of biological samples and have successfully been used in the search for endometriosis markers [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study

Starodubtseva,

Chagovets,

Tokareva

et al. 2024

Preprint

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Endometriosis is a prevalent chronic inflammatory disease characterized by a considerable delay between initial symptoms and diagnosis through surgery. The pressing need for a timely, non-invasive diagnostic solution underscores the focus of current research efforts. This study examines the diagnostic potential of the menstrual blood lipidome. The lipid profile of 39 samples (23 women with endometriosis and 16 patient of control group) was acquired using reverse-phase high-performance liquid chromatography-mass spectrometry with LipidMatch processing and identification. Profiles were normalized based on total ion counts. Significant differences in lipids were determined using the Mann-Whitney test. Lipids for the diagnostic model, based on logistic regression, were selected using a combination of variance importance projection filters and Akaike information criteria. Levels of ceramides, sphingomyelins, cardiolipins, triacylglycerols, acyl- and alkenyl-phosphatidylethanolamines, and alkenyl-phosphatidylcholines increased, while acyl- and alkyl-phosphatidylcholines decreased in cases of endometriosis. PE P-16:0/18:1 and CL 16:0_18:0_22:5_22:6 serve as marker lipids in the diagnostic model, exhibiting a sensitivity of 81% and specificity of 85%. The diagnostic approach based on dried spots of menstrual blood holds promise as an alternative to traditional non-invasive methods for endometriosis screening.

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