Expressions of miRNA-17-92 cluster and mitofusin 2 in endometrial cancer tissues and their clinical significances / 肿瘤研究与临床

ABSTRACT

Objective:To explore the expressions of miRNA-17-92 (miR-17-92) cluster and mitofusin 2 (MFN2) protein in endometrial cancer (EC) and their clinical significances.Methods:A total of 72 EC tissues, 36 endometrial lesions of patients with endometrial atypical hyperplasia, and 22 normal endometrial tissues from total hysterectomy for grade Ⅲ cervical intraepithelial neoplasia in the Second Affiliated Hospital of Shandong First Medical University from January 2008 to December 2014 were collected; at the same time, all patients' paraffin-embedded tissues were collected. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-17-92 in each tissue. Immunohistochemical SP method was used to detect the localization and expression level of MFN2 protein in each paraffin-embedded tissue. The correlation of miR-17-92 and MFN2 protein with clinicopathological features of EC patients was analyzed. Kaplan-Meier method was used to draw survival curve of patients with different miR-17-92 and MFN2 levels, and log-rank test was made; Cox proportional hazard regression model was used for multivariate survival analysis.Results:The relative expression of miR-17-92 in EC, atypical hyperplasia and normal endometrial tissues were 1.49±0.46, 1.01±0.30 and 0.69±0.20, respectively. The expression of miR-17-92 in EC tissues was higher than that in the other endometrial tissues, and the differences were statistically significant (both P < 0.01). The high-expression rates of MFN2 protein in EC, atypical hyperplasia and normal endometrial tissues were 20.8% (15/72), 39.4% (13/33) and 85.0% (17/20); the high-expression rate of MFN2 protein in EC tissue was lower than that in the other endometrial tissues, and the differences were statistically significant (both P < 0.012 5). In EC patients, the relative expression of miR-17-92 in patients with histological type Ⅱ was higher than that in patients with histological type Ⅰ ( P < 0.05); the relative expression of miR-17-92 in patients with myometrial invasion depth ≥1/2 were higher than that in patients with myometrial invasion depth <1/2 ( P < 0.05). The high-expression rate of MFN2 protein in patients with histological type Ⅰ was higher than that in patients with histological type Ⅱ ( P < 0.05); the high-expression rate of MFN2 protein in patients with International Federation of Gynecology and Obstetrics (FIGO) grade Ⅰ was higher than that in patients with FIGO grade Ⅱ and Ⅲ ( P < 0.05). When the EC patients were grouped according to the median relative expression of miR-17-92 (1.421), Kaplan-Meier survival analysis showed that the median overall survival (OS) time of the miR-17-92 low-expression group (36 cases) was not reached, and the high-expression group (36 cases) was 36 months (95% CI 32-42 months), and the difference in OS between the two groups was statistically significant ( P = 0.049); the median OS time of the MFN2 high-expression group (15 cases) was not reached, and the low-expression group (57 cases) was 38 months (95% CI 33-41 months), and the difference in OS between the two groups was statistically significant ( P = 0.046). Multivariate Cox regression analysis showed that the expression levels of miR-17-92 and MFN2 were independent influencing factors for the survival of EC patients ( HR = 3.10, 95% CI 1.36-7.07, P = 0.007; HR = 0.30, 95% CI 0.09-0.99, P = 0.048). Conclusion:The high-expression of miR-17-92 and low-expression of MFN2 protein in EC tissues may be involved in the occurrence and development of EC, and they can be used as indicators for judging the prognosis of EC patients.