The role of survivin in the pathogenesis of endometriosis.

INTRODUCTION: Endometriosis is a common, estrogen-dependent condition, defined as the presence of endometrial-like tissue outside of the uterus, associated with often chronic and inflammatory reaction. The association of endometriosis with cancer is unclear, although endometriosis and cancer present some molecular similarities. Survinin, encoded by the BIRC5 gene, is a protein that controls cell division, inhibits apoptosis and promotes angiogenesis. Here we aimed to summarize and to discuss the main findings of studies that addressed the involvement of survivin in the pathogenesis of endometriosis. EVIDENCE ACQUISITION: We conducted a comprehensive retrieval from electronic databases, included the MEDLINE, EMBASE, with no restrictions to time span. We used the search terms endometriosis and survivin or BIRC5 and collected all relevant studies to explore the association between endometriosis and surviving expression. EVIDENCE SYNTHESIS: A total of 21 studies included in the systematic review, comprising sample collected from 1263 women with endometriosis. Results showed the involvement of more than 60 genes and proteins evaluated in eutopic, ectopic, endometrial and ovarian endometriosis, as well as in several gynecological conditions compared to healthy controls. CONCLUSIONS: The studies provided the basis for the involvement of survivin in the pathogenesis of the disease by several and independent pathways.

BIRC5/Survivin Expression as a Non-Invasive Biomarker of Endometriosis.

The etiology of endometriosis is highly complex, and although it is a benign disease, it has several biological behaviors similar to malignant lesions, including cell invasion, neo-angiogenesis, and decreased apoptosis. Survivin is a protein encoded by the BIRC5 gene that plays a role in cell division by inhibiting apoptosis and regulating the process of mitosis in embryonic and cancer cells. Therefore, we aimed to evaluate the expression of BIRC5 in samples of peripheral blood of women with and without endometriosis. This study comprised of 40 women with endometriosis and 10 healthy women as controls. Peripheral blood samples were collected in the three phases of the menstrual cycle (follicular, ovulatory, and luteal). The expression of the BIRC5 gene was evaluated by RT-qPCR using the TaqMan methodology. The BIRC5 expression was significantly higher in all phases of the menstrual cycle in women with endometriosis, regardless of the disease stage. The accuracy of BIRC5 expression in the peripheral blood for the diagnosis endometriosis presented AUC of 0.887 (p < 0.001), with 97.2% of sensitivity and specificity of 65.5% considering the overall endometriosis group. Regarding the minimal/mild endometriosis group, the AUC presented a value of 0.925 (p < 0.001), with 100% of sensitivity and 79.3% of specificity, whereas in the moderate/severe endometriosis group the AUC was 0.868 (p < 0.001), with a sensitivity of 95.8% and specificity of 65.5%. These findings suggest that the expression of BIRC5 may be a potential noninvasive biomarker for the diagnosis of endometriosis.