Table 2 Candidate biomarkers found by independent teams in at least 3 biological compartments in large cohort
From: An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review
Biomarker | Patients | Potential confunding factors | Type of measured molecule related to the indicated biomarker | Main results | Missing information | Adjustements | Statistics as regards diagnostic accuracy | References | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Control group (n) | Endometriosis group (n) | Age | BMI (endometriosis patients vs controls) | Biological sample type | Global variation (endometriosis patients vs control) | Concerning endometriosis phenotype, cycle phase, hormonal treatments or symptoms | Endometriosis subtype | Cycle phase | Symptoms | Hormonal treatments | AUC | Sensitivity | Specificity | |||
TNF-alpha | Healthy volunteers without detected endometriosis by ultrasound examination (n = 103) | Surgically and histologically proven ovarian endometriosis (n = 190) Stage I/II (n = 77) and III/IV (n = 113) | NS | ND | Protein | Serum | Increased 1.4 times | Cycle phase, treatment for controls, symptoms | Higher in stage III/IV vs I/II | NA | ND or NA | ND or NA | 0.776 (alone) 0.913 (with VEGF, sFlt-1, IL6 and MCP1) | ND (alone) 85.79% (with VEGF, sFlt-1, IL6 and MCP1) | ND (alone) 87.38% (with VEGF, sFlt-1, IL6 and MCP1) | [29] |
Without endometriosis (laparoscopic exam) (n = 93) | Endometriosis patients (n = 201) Stage I/II (n = 132) and III/IV (n = 69) | ND | ND or NA | Protein | Plasma | Reduced 14.6 times | Pain symptoms, lesions localisations | Significant reduction for I/II and III/IV vs controls NS I/II vs III/IV | Change detected in all and secretory phase | ND or NA | NP | 0.758 (all phase) 0.787 (secretory) | 79.5% 80.6% | 73.7% 73.7% | [12] | |
Without endometriosis (laparoscopic exam) (n = 121) | Endometriosis patients (n = 232) Training subset (n = 155), test subset (n = 67) Stage I/II (n = 148) and III/IV (n = 84) US negative (n = 175) | NS | ND or NA | Protein | Plasma | Reduced 1.2 times (only in training set) | Lesions localisations | ND (for stages) | Change detected in all and proliferative phase | ND | NP | 0.65 (for training set US negative patients in follicular phase) | 78% | 57% | [30] | |
Without endometriosis (laparoscopic exam) (n = 35) | Surgically and histologically proven endometriosis (n = 45) Stage I/II/III/IV (n = 10/8/18/9) PE (n = 39), OE (n = 18), DIE (n = 18) | NS | Lower | Protein | Plasma | NS | Pain symptoms other than dysmenorrhea | Higher in patients with vs without DIE | NS (between phase) | NS | ND | ND | ND | ND | [23] | |
Peritoneal fluid | Increased ~ 2 times | |||||||||||||||
Without endometriosis (laparoscopic exam) (n = 59) | Endometriosis (n = 73) Stage I/II (n = 31) and III/IV (n = 42) PE (n = 17), OE (n = 30), DIE (n = 14) | NS | NS or NA | Protein | Peritoneal fluid | NS (All endometriosis) Increased 3.39 times (OE, proliferative phase only) | None | Higher in OE vs DIE (all phases) Higher OE vs PE (proliferative phase) | Main result only found in proliferative phase | ND | NP | ND | ND | ND | [33] | |
Infertile patients undergoing ICSI without endometriosis as assessed by laparoscopy (n = 279) | Surgically and histologically proven endometriosis, infertile patients undergoing ICSI (n = 47) Stage I/II (n = 33) and III/IV (n = 14) | NS | NS | Protein | Follicular fluid | Increased 2 times | Pain symptoms, lesions localisations | ND | NP | NA | NP | ND | ND | ND | [34] | |
Biomarker | Patients | Potential confunding factors | Type of measured molecule related to the indicated biomarker | Main results | Missing information | Adjustements | Statistics as regards diagnostic accuracy | References | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Control group (n) | Endometriosis group (n) | Age | BMI (endometriosis patients vs controls) | Biological sample type | Global variation (endometriosis patients vs control) | Concerning endometriosis phenotype, cycle phase, hormonal treatments or symptoms | Endometriosis subtype | Cycle phase | Symptoms | Hormonal treatments | AUC | Sensitivity | Specificity | |||
MMP-9 or MMP-9/NGAL | Healthy volunteers without endometriosis (laparoscopic exam) (n = 31) | Surgically proven endometriosis (n = 60) OE (n = 31) | NS | NS | Protein | Serum | Increased 1.25 times | Cycle phase and symptoms | Higher in stage III/IV vs I/II | NA | NA | NP | Predictive accuracy of MMP-9 for severe endometriosis (threshold: 14.13 pg/ml) 0.878 | 80% | 73.3% | [79] |
Infertile women without endometriosis but with tubal-factor infertility undergoing IVF (n = 200) | Infertile women with endometriosis confirmed by laparoscopy and histological analysis, undergoing IVF Stage III/IV (n = 140) | NS | NS | Protein | Serum | Increased 1.5 times | Pain symptoms, lesions localisations | NP | NP | NA/NP for infertility | Progesterone supplementation decrease (1.4 times) MMP-9 serum level in pregnant women | ND | ND | ND | [81] | |
Follicular fluid | Increased 1.5 times | |||||||||||||||
Surgically and histologically or clinically verified no evidence of endometriosis (n = 58) | Surgically and histologically verified endometriosis or clinical diagnosis of endometriosis (n = 73) | NA | NA | Protein | Urine | NA | Cycle phase, hormonal treatments, symptoms and lesions localisations | NP | NA | NA | NA | The odds ratio of having MMP-9 or MMP-9/NGAL in the urine and having endometriosis was 7.8 (95% CI: 2.5–25.1; p < 0.001) and 6.3 (95% CI: 1.7–22.8; p < 0.001), respectively | ND | ND | [82] | |
TIMP-1 | Infertile women without endometriosis but with tubal-factor infertility undergoing IVF (n = 200) | Infertile women with endometriosis confirmed by laparoscopy and histological analysis, undergoing IVF Stage III/IV (n = 140) | NS | NS | Protein | Serum | Reduced 1.2 times | Pain symptoms, lesions localisations | NP | NP | NA/NP for infertility | NP | ND | ND | ND | [81] |
Follicular fluid | Reduced 1.2 times | |||||||||||||||
Healthy volunteers without endometriosis (laparoscopic exam) (n = 45) | Surgically proven endometriosis (n = 126) | NA | NA | Protein | Peritoneal fluid | Increased 1.9 times | Pain symptoms, lesions localisations | No statistical difference between stage I/II and III/IV | Increase only in secretory phase | NA/Same range of increase regardless of fertility status | NP | ND | ND | ND | [22] | |
Biomarker | Patients | Potential confunding factors | Type of measured molecule related to the indicated biomarker | Main results | Missing information | Adjustements | Statistics as regards diagnostic accuracy | References | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Control group (n) | Endometriosis group (n) | Age | BMI (endometriosis patients vs controls) | Biological sample type | Global variation (endometriosis patients vs control) | Concerning endometriosis phenotype, cycle phase, hormonal treatments or symptoms | Endometriosis subtype | Cycle phase | Symptoms | Hormonal treatments | AUC | Sensitivity | Specificity | |||
miR-451/miR-451a | Healthy volunteers without endometriosis (laparoscopic exam) (n = 99) | Surgically proven endometriosis (n = 89) Stage I/II/III/IV (n = 27/17/36/19) | NS | NS | miRNA | Serum | Increased 4.5 times (qRT-PCR) | Symptoms, lesions localisations | Significant increase for I/II and III/IV vs controls NS I/II vs III/IV | NS | NA | NS | 0.84 (alone) | 90% | 72.9% | [123] |
0.939 (in combination with miR-125b, miR-150, miR-342, miR-3613 and let-7b) | 83% | 96% | ||||||||||||||
Healthy volunteers without endometriosis (n = 66) | Infertile women with endometriosis confirmed by laparoscopy and histological analysis, undergoing IVF/ICSI (n = 80) Stage I/II (60) and III/IV (20) | NS | NS | miRNA | Serum | Decreased 1.7 times (qRT-PCR) | Other symptoms than infertility for patients, symptoms and treatment for control, cycle phase, lesions localisations | NP | NA | NA | NA | 0,978 | ND | ND | [124] | |
Without endometriosis (laparoscopic exam) (n = 45) | Surgically proven endometriosis (n = 126) | NA | NA | miRNA | Peritoneal fluid | Increased 2.5 times (qRT-PCR) | Pain symptoms, lesions localisations | No statistical difference between stage I/II and III/IV | Significantly up-regulated during menstrual phase compared to proliferative and secretory phase in endometriosis women but not in control | NA/No impact of the fertility status | NP | ND | ND | ND | [22] | |
Infertile women without endometriosis (laparoscopic exam), undergoing IVF (n = 30) | Infertile women with endometriosis confirmed by laparoscopy, undergoing IVF Stage III/IV All with OE (n = 30) | NS | NS | miRNA | Follicular fluid | Decreased 2 times (qRT-PCR) | Pain symptoms | NP | NP | NA/NP for infertility | NP | ND | ND | ND | [126] | |