Background: Ovarian cancer (OC) is a disease characterized by late-stage presentation and poor prognosis. Our aim was to identify a DNA methylation signature for predicting progression-free survival (PFS) of patients with advanced-stage OC.Methods: A bioinformatics analysis was performed to identify methylation sites that are relevant to PFS and develop a DNA methylation signature. A total of 501 patients with advanced-stage OC who were identified from the Cancer Genome Atlas (TCGA) were enrolled as a training cohort, and 108 patients with advanced-stage OC from GSE65820 were used as a validation cohort.Results: A DNA methylation signature was constructed on the basis of five methylation sites. We found that patients with OC in the training and validation cohorts could be stratified, based on the DNA methylation signature, into high- and low-risk groups with distinct prognosis. Different cancer-related pathways were enriched between these two groups. Finally, a nomogram that integrated the methylation signature risk score and clinical stage was established, and the nomogram performed well.Conclusions: The DNA methylation signature provides a promising prognostic biomarker for patients with advanced-stage OC and may help to optimize clinical management.

Background: Propranolol has a significant anti-cancer effect on various cancers. The present study aimed to investigate the underlying mechanism behind the therapeutic effect of Propranolol on the ovarian cancer.Materials and methods: The effect of Propranolol on cell viability was examined by MTT analysis. Cellular apoptosis was evaluated by flow cytometry analysis. Autophagy was defined by autophagosome observed by confocal microscopy after infected with GFP-LC3 adenovirus. In addition, the expression of marker proteins involved in cell apoptosis, autophagy, and ROS/JNK signaling pathway were estimated by Western Blotting assay. Results: Propranolol significantly reduced the viability of human ovarian cancer cell lines SKOV-3 and A2780 in a dose-and time-dependent manner. Flow cytometry analysis revealed that Propranolol induced the cell cycle arrest at G2/M phase and resulted in apoptosis. Moreover, autophagy inhibitor 3-MA markedly enhanced the Propranolol-induced apoptosis. In addition, reactive oxygen species (ROS) was demonstrated dramatically increased after Propranolol treatment and Propranolol activated the phosphorylation of JNK. What is more, p38 inhibitor SB203580 and JNK inhibitor SP600125 attenuated the upregulated expression of LC3-II and cleaved-caspase-3 by the effect of Propranolol. ROS exclusive inhibitor antioxidant N-acetyl cysteine (NAC) weaken the phosphorylation of JNK proteins induced by Propranolol. Conclusions In summary, our results suggested that Propranolol induced cell apoptosis and protective autophagy through the ROS/JNK signaling pathway in human ovarian cancer cells. BackgroundOver the past few decades, ovarian cancer (OC) has become one of the deadliest gynecologic malignancies with the leading cause of cancer-related death among women worldwide, with nearly 140,000 deaths of women occurring every year [1,2]. Cytoreductive surgery and chemotherapeutic drugs are the standard treatment for ovarian cancer. Nowadays, despite significant advances in clinical diagnosis and systemic therapy, the overall 5-year overall survival rate still less than 30% [3]. Therefore, the mechanisms underlying the tumor progression and identification of novel