Ovarian cancer is the deadliest of all gynecologic malignancies. Metastatic ovarian cancer cells exist mainly in the form of multi-cellular spheroids (MCSs) in the ascites of patients with advanced ovarian cancer. We hypothesized that E-cadherin, as an important cell-adhesion molecule, might play an important role in the formation and survival of MCSs. Therefore, we established a three-dimensional suspension culture model of ovarian cancer cells that express high levels of E-cadherin to investigate their growth, proliferation, and resistance to chemotherapeutic drugs by CCK-8 assays. Compared to the cell suspension masses formed by cells with low or absent E-cadherin expression, the MCSs of high E-cadherin SKOV-3 cells had larger volumes, tighter cellular connections, and longer survival times. Although the suspension cell masses of all three cell lines were proliferatively stagnant, possibly due to cell cycle arrest at G1/S, cell mortality at 72 h after cisplatin treatment was significantly decreased in the high E-cadherin SKOV-3 cells compared to SKOV-3 cells without E-cadherin expression and to OVCAR-3 cells with low E-cadherin expression. We conclude, therefore, E-cadherin plays a vital role in MCS formation, maintenance, and drug resistance in ovarian cancer and could be a potential target for late-stage ovarian cancer treatment.

Observational studies assessing the association of dietary fat and risk of ovarian cancer yield discrepant results. Pertinent prospective cohort studies were identified by a PubMed search from inception to December 2015. Sixteen independent case-control and nine cohort studies on dietary fat intake were included, with approximately 900,000 subjects in total. Relative risks (RRs) with 95% confidence intervals were pooled using a random effects model. Heterogeneity, sensitivity analysis and publication bias were assessed; subgroup analysis and analysis stratified by EOC histology were conducted. The reported studies showed a significant increase of ovarian cancer risk with high consumption of total-, saturated-, and trans-fats, while serous ovarian cancer was more susceptible to dietary fat consumption than other pathological subtypes. No evidence of positive association between dietary fat intake and ovarian cancer risk was provided by cohort studies. Menopausal status, hormone replacement therapy, body mass index (BMI), and pregnancy times, modified the objective associations. In conclusion, the meta-analysis findings indicate that high consumption of total, saturated and trans-fats increase ovarian cancer risk, and different histological subtypes have different susceptibility to dietary fat.

Background: The deubiquitinating enzyme (DUB) OTUB1 can regulate the process of ubiquitination, but the influence of OTUB1 on immunity, apoptosis, autophagy, and the prognosis of digestive cancers requires further exploration. Methods: OTUB1 expression was analyzed with the Oncomine and TIMER database. Kaplan-Meier plotter was used to calculate the association between OTUB1 and clinical prognosis. The regulation of OTUB1 on cancer immunocyte infiltration was determined by the TIMER database. The interaction between OTUB1 and immune genes, gene expression profiling (GEP), key genes of apoptosis and autophagy were analyzed via GEPIA. Protein-protein interaction (PPI), gene expression profiling (GEP), and functional pathway enrichment were also performed with the STRING and Pathway Common databases, respectively. Results: High OTUB1 expression was found in CHOL, LIHC, READ, ESCA, and COAD, which was significantly associated with the poorer OS of LIHC (HR = 2.07, 95% CI = 1.30-3.30, P = 0.002), with modifications by sex, stage, grade, and mutant burden. OTUB1 can promote the recruitment of B cells, CD8 + T cells, macrophages in ESCA, B cells, and neutrophils in LIHC. We determined a significant interaction between OTUB1 and USP8, RNF128, LRIG1, UBB, UBC, STAM2, RNF41, EGFR, RPS27A, and HGS by PPI. This functional pathway indicates the regulatory role of OTUB1on immune, apoptosis, and autophagy through its interaction with TP53 and ATG. Conclusions: OTUB1 performed as a molecular indicator of poor prognosis in digestive cancers, regulated the infiltration of tumor immunocytes, and exerted a significant influence on apoptosis and autophagy. OTUB1 is a potential antitumor target for digestive tumors.

BackgroundPrimary squamous cell carcinoma of parotid gland (parotid SCC) is a high malignant histologic subtype of parotid cancers with aggressive clinical presentation. However, the clinical features and survival benefit of postoperative radiotherapy (PORT) for primary parotid SCC are not well known.MethodsA retrospective population-based study was performed to identify the role of PORT in parotid SCC patients diagnosed between 1975 and 2016 from SEER database. A prognostic risk model was established based on patient clinical features, including age, tumor stage, and node involvement status. Patients were stratified into high, intermediate, and low risk according to this model. The survival benefit of radiotherapy was compared in the whole cohort and different risk groups.ResultsNine hundred thirty-one parotid SCC patients were extracted from SEER database, 634 (68.1%) in the RT group and 286 (30.7%) in the non-RT group. Overall, 503 (54.0%) deaths occurred, with a median follow-up of 84 months, the 5-year OS was 43.6% in the whole cohort, 47.7 vs 35.9% in patients with/without PORT (P = 0.005), and 58.9 vs. 38.8 vs. 27.1% in low-, intermediate-, and high-risk group (P < 0.001). Compared with surgery alone, PORT significantly improved the OS of patients with medium risk (47.5 vs. 20.6, P < 0.001), whereas not in the low risk (61 vs. 54%, P = 0.710) and high (25.6 vs. 28.7%, P = 0.524).ConclusionThis prognostic model can separate the patients with parotid squamous cell carcinoma into different risk. PORT significantly improved the OS of patients with intermediate risk, whereas high-risk group may need more intensive treatment strategies.

Background: Radiotherapy (RT) after surgery is a treatment option in the management of parotid adenocarcinoma, and the role of adjuvant RT for parotid adenocarcinoma remains to be clarified. The survival benefit of postoperative radiotherapy (PORT) based on prognostic risk factors needs further determination.Materials and methods: In this retrospective cohort study using SEER data, patients were divided into surgery+RT (RT group) and surgery alone (non-RT group). A prognostic risk model was constructed to stratify patients based on the survival rate. We performed a Cox regression analysis with propensity score weighting to evaluate survival benefit between the two groups. Results: We identified 2223 eligible patients with parotid adenocarcinoma, 1449 (65.2%) in the RT group and 774 (34.8%) in the non-RT group. Overall, 674 cancer-specific deaths occurred over a median follow-up of 141 months, the overall survival (OS) of RT group was better than that of non-RT group in the weighted analysis (HR=0.656, 95% CI=0.487-0.882, P=0.005). Significant survival improvements in the RT group compared with the non-RT group were only observed in patients with high risk (HR=0.647, 95% CI=0.426-0.983, P=0.041). The survival benefit of RT was significantly correlated with prognostic risk stratification (P<.001).Conclusion: In this population-based study, the patient prognostic risk stratification for parotid adenocarcinoma is associated with the magnitude of survival improvement by RT after surgery, suggesting that this risk model could provide decision guidance on comprehensive treatment strategy.