Biomarcadores en endometriosis

Abstract

BACKGROUND: Endometriosis causes impaired quality of life and chronic pelvic pain, especially in young women. The diagnosis delay is around 7 years due to the lack of diagnostic tools, which causes negative impact in patient’s welfare and fertility, and has high economic and social costs. Recurrence is also the other priority in endometriosis research because up to 40-50% of patients recurs in the following 5 years after the surgery. Consequently, the detection of these patients could let an appropriate follow-up that would be beneficial for them. There is an unmet clinical need in the identification of novel techniques that provide earlier diagnosis and prognostic tools to decrease associated comorbidity. In this context, we hypothesized that angiogenesis may play an important role in endometriosis pathogenesis. OBJECTIVE: Analyze the expression of angiogenic factors in plasma, endometrial biopsy and endometriotic tissue to identify potential biomarkers for endometriosis diagnosis and prognosis. STUDY DESIGN: In this prospective case-control study, 77 women suffering from endometriosis (with histological confirmation of the disease) and 103 healthy controls without endometriosis were recruited in the Vall d’Hebron Hospital (Barcelona, Spain) between 2014 and 2020. Plasma samples were analyzed for protein expression levels of endoglin, sFlt-1 and PlGF using commercially available ELISA kits. Tissue samples from endometrial biopsy and endometriotic tissue were analyzed and RNA expression of endoglin (Eng), soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PlGF) was assessed by real-time polymerase chain reaction. RESULTS: In plasma samples, sFlt-1 was upregulated in endometriosis and presented an AUC value of 0.78 as a diagnostic biomarker. No differences were observed in endoglin and PlGF. In endometrial biopsy, all assessed biomarkers were significantly lower in endometriosis in comparison to the control group. The angiogenic activity in uterine aspirate was similar among adenomyosis, deep-ovarian endometriosis, and organ involvement. Although there were no statistical differences between recurrent and non-recurrent endometriosis, there was a tendency for downregulation of Eng, sFlt-1 and PlGF in the recurrence endometriosis group. In tissue samples, all angiogenic factors were upregulated in endometriosis, including different subtypes (deep and ovarian endometriosis). The analysis of recurrence in the primary endometriosis showed an increased levels of angiogenic factors in those patients with recurrence and showed AUC values ranging from 0.75 to 0.87 as a prognostic biomarkers. CONCLUSIONS: sFlt-1 could be a diagnostic biomarker in plasma samples. All studied biomarkers have demonstrated high accuracy for endometriosis diagnosis in endometrial biopsy. Hence, there was no correlation with the severity of the disease. Endoglin, sFlt-1 and PlGF might be prognostic biomarkers predicting recurrence in ectopic endometrial tissues. In all simples, we could not predict the severity or subtypes of the disease by analyzing expression of Eng, sFlt-1 y PlGF.