PRMT5 has been reported to be involved in the processes of tumor progression at various steps. The aim of this study was to examine the role of PRMT5 in epithelial ovarian cancer (EOC). In this study, PRMT5 and Ki-67 expression were examined by immunohistochemistry (IHC) in cohorts of normal, benign, and cancerous ovarian tissues. PRMT5 overexpression was observed in 83.1% (98/118) of EOCs, and it was significantly associated with serous type, poor differentiation, advanced tumor stage, lymph node invasion, presence of residual tumor, and high expression of Ki-67 ( p<0.05, respectively). Moreover, overexpression of PRMT5 was an independent prognostic marker for decreased overall survival and progression-free survival in univariate survival analysis and multivariate Cox regression analysis. In ovarian cancer cell lines A2780 and SKOV3, PRMT5 knockdown by siRNA inhibited cell growth/proliferation and induced apoptosis via upregulation of E2F-1. These results suggest that overexpression of PRMT5 correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for EOC. Thus, PRMT5 may represent a clinically effective new target for therapy of ovarian cancer.
Overwhelming evidence has demonstrated that the aberrant expression of the human trophoblast cell-surface antigen (TROP2) was associated with tumor aggressiveness and poor prognosis in a variety of human cancers, however the roles of TROP2 in cervical cancer have not been investigated. The purpose of our study was to elucidate the prognostic significance of TROP2 expression in patients with cervical cancer and determine its effect on tumor progression. Immunohistochemistry assay showed that 88.7% (94/106 cases) of cervical cancer specimens were positively stained with TROP2, and the overexpression of TROP2 was closely related with FIGO stage, histological grades, lymphatic metastasis, invasive interstitial depth and high expression of Ki-67. Patients with TROP2-positive staining exhibited a significantly decreased overall survival and progression free survival; it was also an independent predictor for prognosis according to multivariate analysis. Moreover, down-regulation of TROP2 mediated by siRNA in Siha and CaSki cells resulted in a strong inhibition of proliferation and invasion, TROP2 abrogation also elevated the apoptotic ratio and caused G1 arrest. Conversely, enforced expression of TROP2 in HeLa and C33A cells remarkably promoted cell growth, migration and invasion. In addition, the tumorigenic function of TROP2 was associated with the increased expressions of cyclin D1, cyclin E, CDK2 and CDK4 but reduced expression of p27 and E-cadherin via the activation of Erk1/2 signaling pathway. Furthermore, the inhibition of TROP2 expression in cervical cancer cell lines enhances sensitivity to cisplatin. The present study suggest that overexpression of TROP2 may play crucial roles in the development and pathogenesis of human cervical cancer, therefore, TROP2 may represent a prospective prognostic indicator and a potential therapeutic target of cervical cancer.
0.17–2% of mature cystic teratoma of the ovary (MCTO) undergo malignant transformation, of which 80% are squamous cell carcinoma (SCC) transformation in MCTO. We aim to investigate the clinical characteristics and treatment of SCC transformation in MCTO We systematically searched PubMed database and individual patient data about SCC transformation in MCTO were extracted. The published cases were combined with 6 cases of SCC transformation in MCTO from Qilu Hospital, Shandong University. The incidence of SCC transformation in MCTO was 0.3%. A total of 435 cases of SCC transformation in MCTO were enrolled in the analysis. The mean age of diagnosis was 53.5 (range 19–87) years old. The most common clinical manifestations were abdominal pain (47.3%) and abdominal mass (26.0%). StageI,II, III and IV accounted for 50.0, 18.8, 26.8 and 4.4% of all cases, respectively. Patients with stage I had significantly better prognosis than stage II, III and IV patients (P < 0.01). Hysterectomy can improve overall survival (P < 0.01). For patients younger than 45 years old with stageIA orIC, there was no difference in mortality between fertility-sparing and radical surgery (P = 1.00). Adjuvant chemotherapy can improve survival in patients with advanced stage (P = 0.02), and chemotherapy with platinum was related to better prognosis (P = 0.02). SCC transformation in MCTO is a rare malignancy mainly occurs in older age. FIGO stage is an independent prognostic factor. Hysterectomy and platinum-based chemotherapy are associated with better survival. Fertility-sparing surgery is feasible for young patients with early stage.
1 June 2017 in Biochemical and Biophysical Research Communications
The aim of this study was to illuminate risks factors of residual lesions, and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive margin who underwent cervical conization. A retrospective cohort study of 218 patients with positive margin after conization, including cold knife conization (CKC) and loop electrosurgical excisional procedure (LEEP), and follow-up from 2013 through 2016. The diagnosis of residual disease and recurrence were established and confirmed by biopsy. We evaluate the correlations among residual rate, recurrence rate, and clinical parameters, such as age, menopausal status, gravity, parity, glandular involvement, thinprep cytologic test (TCT), and human papillomavirus (HPV) results. We also detect the difference between CKC and LEEP. There was statistical difference between the positive margin rate of CKC group and LEEP regarding the surgery methods (5.8% and 12.09% separately, P < .001). Residual disease was found in 53.66% cases where 41 patients received second surgery after conization. Besides, age (P = .027), menopausal status (P = .006), and HPV infection (P = 0.018) were significantly associated with residual lesion. Among 177 cases with histopathologic follow-up, 15.91% women relapsed from 4 to 27 months. As for recurrence we found it was more frequent with HPV infection and glandular involvement (P < .001). TCT was also an independent factor in patients with recurrence of lesion. No evidence shows difference between CKC and LEEP for recurrence rate (P = .918). The factors related to rate of residual lesion were age, menopausal status, and HPV infection. HPV infection, TCT, and glandular involvement were associated with HSIL recurrence. LEEP was as effective as CKC with regard to recurrence rate. Further large-scale studies are needed to confirm our findings.
An accumulated evidence supports that MicroRNAs (miRNAs) have shown a prominent role in pathological processes and different tumor onset. However, to date, the potential functional roles and molecular mechanisms by how microRNA-424-5p(miR-424-5p) affects cancer cell proliferation are greatly unclear, especially in epithelial ovarian cancer(EOC).In this study, we demonstrated that miR-424-5p was significantly down-regulated in EOC tissues and cell lines. The level of miR-424-5p was negatively correlated with tumor size, TNM stage, pathological grade, lymphatic metastasis of EOC. Restoring miR-424-5p expression in EOC cells dramatically suppressed cell proliferation and caused an accumulation of cells in G1 phase, and thus contributed to better prognosis of EOC patients. Mechanistically, miR-424-5p inhibits CCNE1 expression through targeting CCNE1 3′UTR, and subsequent arrest cell cycle in G1/G0 phase by inhibiting E2F1-pRb pathway. This study revealed functional and mechanistic links between miR-424-5p and CCNE1 in the progression of EOC and provide an important insight into that miR-424-5p may serve as a therapeutic target in EOC.