Table 2.
Potential biomarkers found in extracellular vesicles (exosome-like vesicles) of different biological origins from patients with different stages of endometriosis
| Types of molecule | Potential biomarker(s) | Biological origin | Comparision | EV isolation method | EV characterization techniques | Detection technique | Sample size | Endometriosis stage | Total number differentially expressed | Reference | Year of publication | Complete reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| miRNAs |
↑ miR-342-5p, miR-130b-3p, miR-210-3p ↓ miR-132-5p, miR-335-3p |
Uterin cavity fluid | Endo vs Control | Exosome isolation kit (Echobiotech) | TEM, NTA, WB | RNASeq | 4 endo, 4 ctrl | All patients III-IV |
7 upregulated 2 downregulated |
PMID: 36,551,866 | 2022 | Jiang Y, Chai X, Chen S, Chen Z, Tian H, Liu M, Wu X. Exosomes from the Uterine Cavity Mediate Immune Dysregulation via Inhibiting the JNK Signal Pathway in Endometriosis. Biomedicines. 2022 Dec 2;10(12):3110. https://doi.org/10.3390/biomedicines10123110. PMID: 36,551,866; PMCID: PMC9775046 |
| miRNAs |
↑ miR-6795-3p, miR-146b-3p, miR-32-3p ↓ miR-128–1-5p, miR-215-5p, miR-26b-5p |
Serum | Endo vs Control | Exosome binding enhancer and magnetic beads | TEM, WB | Microarray | 4 endo, 4 ctrl | 1 patients I-II, 3 patients III-IV |
26 upregulated 19 downregulated |
PMID: 34,542,679 | 2022 | Wu Y, Yuan W, Ding H, Wu X. Serum exosomal miRNA from endometriosis patients correlates with disease severity. Arch Gynecol Obstet. 2022 Jan;305(1):117–127. https://doi.org/10.1007/s00404-021-06227-z. Epub 2021 Sep 20. PMID: 34,542,679; PMCID: PMC8782809 |
| proteins |
↑ RAN, FTH1, UBB ↓ HEL70, MMP2, HEL-S-1 |
Endometrium and endometriotic lesions | Endo vs Control | Ultracentrifugation | TEM, NTA, WB | LS-MS/MS | 6 endo, 10 ctrl | Not reported |
3 upregulated 6 downregulated |
PMID: 35,557,941 | 2022 | Abudula M, Fan X, Zhang J, Li J, Zhou X, Chen Y. Ectopic Endometrial Cell-Derived Exosomal Moesin Induces Eutopic Endometrial Cell Migration, Enhances Angiogenesis and Cytosolic Inflammation in Lesions Contributes to Endometriosis Progression. Front Cell Dev Biol. 2022 Apr 26;10:824,075. https://doi.org/10.3389/fcell.2022.824075. PMID: 35,557,941; PMCID: PMC9086167 |
| circRNAs, miRNAs and mRNAs |
qRT-PCR: ↑ circ_002612309 (ectopic vs ctrl/eutopic) ↓ miR-15a-5p (eutopic/ectopic vs ctrl) ↑ ATP6V1A (eutopic/ectopic vs ctrl) |
Endometrium and endometriotic lesions | Overlapping DEGs between Ectopic vs Ctrl, Eutopic vs Ctrl and Ectopic vs Eutopic | ExoQuick-TC (System Biosciences) | TEM, NTA, WB | RNASeq | 3 endo (3 eutopic, 3 ectopic samples), 3 ctrl | All patients III-IV |
circRNAs: 2915 upregulated 640 downregulated miRNAs: 17 upregulated 9 downregulated mRNAs: 550 upregulated 136 downregulated |
PMID: 33,901,012 | 2021 | Wu J, Fang X, Huang H, Huang W, Wang L, Xia X. Construction and topological analysis of an endometriosis-related exosomal circRNA-miRNA-mRNA regulatory network. Aging (Albany NY). 2021 Apr 26;13(9):12,607–12630. https://doi.org/10.18632/aging.202937. Epub 2021 Apr 26. PMID: 33,901,012; PMCID: PMC8148458 |
| miRNAs |
↑ miR-615-3p, miR-6873-3p, miR-3195 ↓ miR-1273 h-3p, miR-4262, miR-1269a |
Eutopic endometrium from patients with endometriosis and normal endometrium | Endometriotic lesions vs Ctrl | ExoQuick-TC (System Biosciences) | TEM, FC, NTA | RNASeq | 3 endo, 3 ctrl | All patients II-IV |
26 upregulated 23 downregulated |
PMID: 32,593,507 | 2020 | Zhou W, Lian Y, Jiang J, Wang L, Ren L, Li Y, Yan X, Chen Q. Differential expression of microRNA in exosomes derived from endometrial stromal cells of women with endometriosis-associated infertility. Reprod Biomed Online. 2020 Aug;41(2):170–181. https://doi.org/10.1016/j.rbmo.2020.04.010. Epub 2020 May 3. PMID: 32,593,507 |
| miRNAs |
↑ miR-197-5p, miR-22-3p, miR-320a ↓ miR-134-5p, miR-3141, miR-4499 |
Serum | Endo vs Control | Differential centrifugation | TEM, NTA, WB | Microarray | 5 endo, 5 ctrl | Not reported |
18 upregulated 6 downregulated |
PMID: 32,076,458 | 2020 | Zhang L, Li H, Yuan M, Li D, Sun C, Wang G. Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis. Dis Markers. 2020 Jan 23;2020:2,456,340. https://doi.org/10.1155/2020/2456340. PMID: 32,076,458; PMCID: PMC7008302 |
| proteins | PRDX1, H2A type 2-C, ANXA2, ITIH4 and tubulin a-chain | Peritoneal fluid | Endo I/II vs Endo III/IV vs Ctrl | Exo-spin size-exclusion chromatography columns (Cell Guidance Systems) | TEM, NTA, WB | LC–MS/MS | 16 endo I/II, 6 endo III/IV and 6 ctrl | Patients split I/II and III/IV | 5 proteins exclusively found in endo | PMID: 32,106,990 | 2020 | Nazri HM, Imran M, Fischer R, Heilig R, Manek S, Dragovic RA, Kessler BM, Zondervan KT, Tapmeier TT, Becker CM. Characterization of exosomes in peritoneal fluid of endometriosis patients. Fertil Steril. 2020 Feb;113(2):364–373.e2. https://doi.org/10.1016/j.fertnstert.2019.09.032. PMID: 32,106,990; PMCID: PMC7057257 |
| miRNAs |
↑ miR-1908-5p, miR-130b-5p, miR-4488 ↓ miR-6508-3p, miR-145-5p, miR-365b-3p |
Peritoneal fluid | Early endo, late endo vs Ctrl | Ultracentrifugation | None | RNASeq | 3 early stage endo, 3 advanced stage endo and 3 ctrl | Patients I-IV |
early vs ctrl: 130 upregulated 43 downregulated late vs ctrl: 87 upregulated 63 downregulated |
PMID: 30,453,861 | 2019 | Chen Y, Wang K, Xu Y, Guo P, Hong B, Cao Y, Wei Z, Xue R, Wang C, Jiang H. Alteration of Myeloid-Derived Suppressor Cells, Chronic Inflammatory Cytokines, and Exosomal miRNA Contribute to the Peritoneal Immune Disorder of Patients With Endometriosis. Reprod Sci. 2019 Aug;26(8):1130–1138. https://doi.org/10.1177/1933719118808923. Epub 2018 Nov 19. PMID: 30,453,861 |
| miRNAs |
↑ miR-27a-3p ↓ miR-375, miR-30d-5p (endometrium, lesions and plasma) |
Endometrium, endometriotic lesions and plasma | Eutopic vs Ectopic, Ectopic vs Ctrl and Eutopic vs Ctrl | miRCURY exosome isolation kit (Qiagen) | TEM, WB | RNASeq | 6 endometrium, 6 endometriotic lesions and 6 plasma | All patients III-IV |
Plasma: 21 DE Ectopic/Eutopic samples: 14 DE |
PMID: 31,534,048 | 2019 | Khalaj K, Miller JE, Lingegowda H, Fazleabas AT, Young SL, Lessey BA, Koti M, Tayade C. Extracellular vesicles from endometriosis patients are characterized by a unique miRNA-lncRNA signature. JCI Insight. 2019 Sep 19;4(18):e128846. https://doi.org/10.1172/jci.insight.128846. PMID: 31,534,048; PMCID: PMC6795291 |
| lncRNA | ↑ circulating exosomal aHIF and exosomal ectopic endometrium | Endometrium, endometriotic lesions and plasma | Eutopic vs Ectopic, Ectopic vs Ctrl and Eutopic vs Ctrl | Total Exosome Isolation kit (Invitrogen) for cell culture and ExoQuick exosome precipitation solution kit for serum | TEM, WB | qRT-PCR | 30 endo and 16 ctrl | All patients III-IV | Single gene assessment | PMID: 30,808,247 | 2019 | Qiu JJ, Lin XJ, Zheng TT, Tang XY, Zhang Y, Hua KQ. The Exosomal Long Noncoding RNA aHIF is Upregulated in Serum From Patients With Endometriosis and Promotes Angiogenesis in Endometriosis. Reprod Sci. 2019 Dec;26(12):1590–1602. https://doi.org/10.1177/1933719119831775. Epub 2019 Feb 26. PMID: 30,808,247 |
| miRNAs |
qRT-PCR: ↑ miR-21-5p |
Endometrium and endometriotic lesions | Endometriotic lesions vs Ctrl | Total Exosome Isolation kit (Invitrogen) | TEM, NTA | Targeted qRT-PCR | 5 endo (5 eutopic, 5 ectopic samples), 5 ctrl | Not reported | Non applicable | PMID: 26,841,879 | 2016 | Harp D, Driss A, Mehrabi S, Chowdhury I, Xu W, Liu D, Garcia-Barrio M, Taylor RN, Gold B, Jefferson S, Sidell N, Thompson W. Exosomes derived from endometriotic stromal cells have enhanced angiogenic effects in vitro. Cell Tissue Res. 2016 Jul;365(1):187–96. https://doi.org/10.1007/s00441-016-2358-1. Epub 2016 Feb 3. PMID: 26,841,879; PMCID: PMC4917586 |