RESUMO
As an integral component of the surgical staging system, lymphadenectomy for patients with endometrial cancer (EC) remains controversial, particularly in clinical stage I disease that includes not only low-risk, but also high-risk subgroups. In order to maximize the therapeutic effect of lymph node excision for high-risk patients who can potentially obtain survival benefits from it while minimizing its reverse effects in low-risk patients, pre-operative risk stratification of lymph node metastasis is necessary. The upregulation of microRNA-205 (miR-205) in carcinoma of the endometrium has been consistently reported recently and has been found to correlate with poor survival. The current study aimed to investigate whether the overexpression of miR-205 in curettage samples of EC could identify patients who are at a high risk for lymph node metastasis prior to surgery and validate the role of miR-205 as a prognostic marker in EC. Relative quantification detection of miR-205 in curettage and hysterectomy specimens of patients with EC was performed. Prediction of lymph node metastasis based on miR-205 expression, as well as tumor type and grade in curettage samples, was performed for all EC patients and patients with clinical stage I disease. Moreover, survival analysis was conducted. It was observed that miR-205 was significantly and consistently elevated in the curettage and hysterectomy samples of EC relative to normal controls. Furthermore, the overexpression of miR-205 could predict lymph node metastasis with a high accuracy and was revealed again to be associated with a poor prognosis in EC. Prospective and multicentric studies are required to further clarify the value of miR-205 as a promising predictor to stratify risk for lymph node metastasis in EC.
RESUMO
BACKGROUND: Endometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration. METHODS: We performed primary culture of EECs and investigated the expression of OPN and MMP-9 in EECs regulated by 17beta-estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and to explore the corresponding change in MMP-9 expression. Real-time RT-PCR, western blot analysis and flow cytometry were used to determine the expression levels of OPN and MMP-9. Gelatin zymography was performed to observe the enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch assays were performed to investigate the migration ability of EECs. RESULTS: The expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those in EECs from patients with endometriosis (EEECs). The expression levels of OPN and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA interference. Active MMP-9 expression increased with E2 treatment and decreased with siRNA treatment in EEECs compared with the same treatments in NEECs. The migratory abilities of EEECs were enhanced after cells were treated with E2; in contrast, these abilities were reduced by siRNA interference. In NEECs, active MMP-9 and cellular migration abilities were only minimally influenced by E2 and siRNA treatment. CONCLUSIONS: The present study suggests that the up-regulation of MMP-9 via activation of OPN induced by estrogen may correlate with the migration of endometrial epithelial cells in patients with endometriosis.
