Ovarian cancer is the most lethal gynecological malignancy. Recurrence and chemoresistance are tough challenges leading to poor prognosis. HJURP is a molecular chaperone of CENP-A, which is associated with aggressive progression in multiple tumors. However, the function of HJURP in ovarian cancer has not been elucidated. In our study, we found HJURP was over-expressed in ovarian cancer and high expression of HJURP was correlated to unfavorable prognosis. HJURP knockdown could inhibit proliferation, metastasis and induce G0/G1 stagnation of ovarian cancer cells. Besides, next-generation sequencing (NGS) unveiled that WEE1 was down-regulated by silencing HJURP. Further mechanistic research revealed that HJURP regulated WEE1 through MYC, and luciferase assay indicated that MYC was a transcription factor of WEE1. Additionally, we investigated that silencing HJURP increased sensitivity of ovarian cancer cells to cisplatin via MYC/WEE1 axis, and HJURP participated in DNA repair of cisplatin-induced damage. More interestingly, silencing HJURP could enhance sensitivity of ovarian cancer cells to AZD1775 and improve the synergistic effect of cisplatin plus AZD1775 combined therapy. Collectively, our data displays that HJURP promotes tumor progression and chemoresistance of ovarian cancer, and HJURP has potential to be a novel therapeutic target in the combined treatment with cisplatin and AZD1775 in ovarian cancer.

BackgroundThe treatment and prognostic factors of intravenous leiomyomatosis (IVL) remain lacking systematic evidence.MethodsA retrospective study was conducted on IVL patients from the Qilu Hospital of Shandong University, and IVL cases were published in PubMed, MEDLINE, Embase and Cochrane Library databases. Descriptive statistics were used for the basic characteristics of patients. The Cox proportional hazards regression analysis was used to assess the high-risk factors related to the progression-free survival (PFS). The comparison of survival curves was performed by Kaplan–Meier analysis.ResultsA total of 361 IVL patients were included in this study, 38 patients from Qilu Hospital of Shandong University, and 323 patients from the published literature. Age ≤45 years was observed in 173 (47.9%) patients. According to the clinical staging criteria, stage I/II was observed in 125 (34.6%) patients, and stage III/IV was observed in 221 (61.2%) patients. Dyspnea, orthopnea, and cough were observed in 108 (29.9%) patients. Completed tumor resection was observed in 216 (59.8%) patients, and uncompleted tumor resection was observed in 58 (16.1%) patients. Median follow-up period was 12 months (range 0–194 months), and 68 (18.8%) recurrences or deaths were identified. The adjusted multivariable Cox proportional hazard analysis showed age ≤45 years (vs. >45) (hazard ratio [HR] = 2.09, 95% confidence interval [CI] 1.15–3.80, p = 0.016), and uncompleted tumor resection (vs. completed tumor resection) (HR = 22.03, 95% CI 8.31–58.36, p < 0.001) were high-risk factors related to the PFS.ConclusionPatients with IVL have a high probability of recurrence after surgery and a poor prognosis. Patients younger than 45 years and with uncompleted tumor resection are at higher risk of postoperative recurrence or death.

High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological malignancies; however, the precise molecular mechanisms have not been fully characterized. Fibulin-5 (FBLN-5) is an extracellular matrix (ECM) glycoprotein, and plays a crucial role in maintaining the stability of ECM structures, regulating cell proliferation and tumorigenesis. In the present study, the expression of FBLN-5, as determined by western blot analysis and immunohistochemistry, was significantly increased in normal fallopian tube (FT) samples compared with that in HGSOC samples, and decreased FBLN5 expression was associated with unfavorable prognosis of HGSOC. Functional characterization revealed that FBLN5 overexpression significantly inhibited migration, invasion and proliferation abilities of ovarian cancer cells in vitro. Furthermore, micro (mi)RNA-27a-3p (miR-27a-3p) was revealed to be increased in HGSOC, and dual-luciferase reporter assay indicated that miR-27a-3p was functioned as a negative regulator of FBLN5 by directly binding with its 3'-untranslated region. Collectively, FBLN5 expression was associated with prognosis, proliferation, and metastasis in HGSOC. We hypothesized that FBLN5 was targeted by miR-27a-3p and may serve as a biomarker and provide a new therapeutic approach for the treatment of HGSOC.

Metastasis of OC is the most common cause of disease-associated mortality. In the majority of cases, the disease has spread beyond ovaries at the time of diagnosis. 1 Metastasis is a dynamic, multistep and complex process, including escaping from primary tumor, spreading in the systemic circulation, extravasation at distant tissues, and organ seeding. 2 Among diverse metastatic routes, peritoneal implantation is the most common mode of metastasis for OC. 3 At the cellular level, cancer cells exfoliated from the primary site to a fluid-filled peritoneal cavity where they exist in suspension as single cells or MCSs. OC MCSs contribute to the production and accumulation of large amounts of malignant ascites and are the major seeds of peritoneal metastasis. 4 Therefore, improved understanding of properties, underlying molecular mechanisms of the cellular biology of OC MCSs will shed light on novel therapeutic options.

Objective: This study assessed the effect of omentectomy on the prognosis and fertility in patients with clinically early-stage (I, II) malignant ovarian germ cell tumours (MOGCT).Design: A retrospective multicentre study. Setting: Four university teaching hospitals in China.Population: A total of 268 patients with clinically apparent early-stage (I, II) MOGCT.Methods: Data were obtained from the medical records. Additionally, the propensity score matching (PSM) algorithm was adopted.Main outcome measures: Prognostic outcomes were disease-free survival (DFS) and overall survival (OS). Fertility outcomes were pregnancy and live birth rates.Results: A total of 187 (69.8%) patients underwent omentectomy. Kaplan-Meier analysis showed no significant differences in DFS and OS between the omentectomy and non-omentectomy groups before and after PSM (p > 0.05). Additionally, subgroup analysis stratified by age (<18 and ≥18 years) showed similar results. International Federation of Gynecology and Obstetrics (FIGO) stage was the only risk factor associated with DFS (hazard ratio [HR] 14.71, 95% confidence interval [CI] 4.47-48.38, p < 0.001) and OS (HR 37.36,, p = 0.002). Pregnancy and live birth rates in the total population were 80.3% and 66.7%, respectively. There were no significant differences between the two groups before and after PSM. Conclusions: Omentectomy did not improve survival or affect fertility in patients with clinically apparent early-stage (I, II) MOGCT, regardless of the age. The clinical FIGO stage was an independent risk factor for recurrence and death. K E Y W O R D S clinically apparent early stage, malignant ovarian germ cell tumours, omentectomy, prognostic outcomes, propensity score matching, reproductive outcomes