The aim of the study is to increase the effectiveness of complex treatment of external genital endometriosis by creating an algorithm taking into account the characteristics of cell-molecular markers. The novelty of the study and the results. For the first time the molecular genetic marker such as let-7 miRNA was included in the complex of examination of women with external genital endometriosis and a new algorithm was used to select the optimal treatment tactics for patients with this pathology. For the first time, the comparison of sensitivity, specificity and prognostic value was performed for such non-invasive biomarkers in the blood of patients with EGE as CA-125 and let-7 miRNA and mir-9 miRNA. Mann-Whitney analysis showed a significant difference in let-7 miRNA levels between groups of patients with endometriosis and patients in the control group. At the same time, another representative biomarker miRNA mir-9 in a similar analysis between groups of patients with endometriosis and the control group, as well as between groups with clinically and histologically severe and mild endometriosis did not give a statistically significant difference.
Given into account that the cancer antigen CA-125 is used to diagnose endometriosis ovarian cysts, we performed the analysis of sensitivity, specificity, positive and negative prognostic values. Based on promising data obtained from correlation analysis and groups comparisons using Mann-Witney criteria, we decided to perform the ROC analysis. The following indicators has been calculated in our ROC analysis of miRNA let-7 and also for CA-125. For miRNA let-7 sensitivity was 92.563, specificity - 82.545, PPV - 93.912, NPV - 79.234. Indicators of the classification model for CA-125 were: sensitivity - 86.105, specificity -76.422, PPV - 91.397, NPV- 65.406. We’ve seen from the ROC analysis that flat under curve for miRNA let-7 is higher than for CA-125. Thus, miRNA let-7 has the best parameters (sensitivity, specificity, predictive value of positive and negative results). Comparison with Ca-125 using ROC analysis showed the presence of the larger area under the curve, it indicates great prospects for this marker, which may be used for early diagnosis of endometriosis.
The practical significance of the results. The developed algorithm with the inclusion of a new non-invasive biomarker allows to improve the diagnosis of this disease and choose an effective method of treatment in the early stages of the disease, let-7 miRNA has better sensitivity, specificity, positive and negative prognostic values showed its advantages over other EGE biomarkers, so it was chosen by us for comparison. The median value of let-7 miRNA was 4.43, when analyzing the mean values of the indicator and comparing endometriosis group 1 (mild and moderate) and endometriosis group 2 (moderate and severe endometriosis), we obtained an average value of 3.96 in the latter group, thus the indicator let-7 "4" was chosen for use in the new algorithm.
To test the effectiveness of the algorithm, a study was conducted on 32 women with PGI, treatment tactics were determined taking into account the indicator of a new biomarker (group 3, n = 32). Results compared with the group of patients with EGE in the main part of the study, all women from whom underwent laparoscopic treatment without taking into account the indicators of let-7 miRNA in the blood (group 1 + 2, n = 64). We determined the significance of the difference between the studied groups using t-test (Student's criteria). This allowed us to make the correct distribution of data in the study groups. The study of the distribution was carried out by the Shapiro-Wilk method. According to the results of p-value calculation for comparison groups on such indicators as VAS, AMH, AFC, age, BMI, CA-125 level (IU / ml), the level of miRNA let-7 – groups wasn’t statistically different. A statistically significant difference between these groups was found in the indicator "Time to treatment" (p = 0.001). After that, the results of treatment in both groups were evaluated. In group 1 + 2, due to the fact that all patients had the surgical treatment, we noted a decrease in ovarian reserve -AMH and AFC in 1.8 times, which is a negative fact, and indicators of the intensity of pain (VAS scores) were significantly reduced, which can be assessed as a positive effect of treatment. To comparing the results before and after treatment in the test group of the algorithm there was no difference in ovarian reserve due to reduced frequency of surgical treatment, use of modified sclerotherapy techniques and ART methods, while the effect of treatment as a significant difference in pain intensity was achieved. This once again proves the need for a differentiated approach to the selection of treatment for external genital endometriosis, taking into account additional non-invasive biomarkers.
