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Altered expression of prostate tumor overexpressed-1 (PTOV1) is observed in various types of human cancers. However, the role of PTOV1 in epithelial ovarian cancer (EOC) remains unclear. PTOV1 messenger (m)RNA expression in EOC patients was evaluated by quantitative real-time PCR (qRT-PCR). PTOV1 protein expression was also analyzed in archived paraffin-embedded EOC tissues using immunohistochemistry (IHC), and its association with overall survival of patients was analyzed by statistical analysis. Results from qRT-PCR analysis show that the expression level of PTOV1 mRNA was significantly higher in tumor tissues of EOC, compared to that in adjacent noncancerous tissues (P < 0.001). IHC staining showed that high expression of PTOV1 was detected in 57.2 % (87/152) of EOC cases. High expression of PTOV1 was significantly associated with pathological grade (P = 0.029) and clinical stage (P = 0.001). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of PTOV1 resulted in a significantly poor prognosis of EOC patients. Multivariate analysis showed that high expression of PTOV1 was an independent prognostic factor for overall survival (P < 0.001). In conclusion, PTOV1 protein abnormal expression might contribute to the malignant progression of EOC. High expression of PTOV1 predicts poor prognosis in patients with EOC.

Background Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. Methods CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. Results Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs . 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs . 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. Conclusion Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

Background:The effect of low serum vitamin E levels on the risk of colorectal cancer (CRC) remains inconclusive. This meta-analysis aims to synthesize relevant studies to evaluate the association between serum vitamin E and the risk of CRC based on case–control studies.Methods:Potentially relevant studies were selected by searching PubMed, EMBASE, and China National Knowledge Infrastructure databases according to inclusion and exclusion criteria. The association between serum vitamin E levels and CRC was estimated by the weighted mean difference (WMD) and 95% confidence interval (CI) using a random-effects model. Heterogeneity was evaluated using Q test and I2 statistic. Subgroup analysis was conducted to explore sources of heterogeneity. Sensitivity analysis was performed to reveal stability and reliability.Results:A total of 10 papers with 11 studies, including 6431 subjects with 520 CRC patients and 5981 controls, were included in this present meta-analysis. The results indicated that compared with healthy controls, patients with CRC showed lower concentrations of serum vitamin E (WMD = −2.994 μmol/L, 95% CI = −4.395 to −1.593). Ethnicity subgroup analysis indicated that the serum vitamin E levels were lower in European (WMD = −1.82 μmol/L, 95% CI = −3.00 to −0.65), but not in Asian. Control-source subgroup analysis revealed that a significant association was observed in subgroup with hospital-based controls (WMD = −3.43 μmol/L, 95% CI = −6.27 to −0.59), but not in those with population-based controls. Sensitivity analysis suggested no significant difference in the pooled estimates, indicating stable results.Conclusions:CRC is associated with a lower concentration of serum vitamin E. However, necessary prospective cohort studies should be conducted to assess the effect of serum vitamin E on the risk of CRC in the future.

Enhancer of zeste homolog 2 (EZH2) is abnormally highly expressed in pancreatic cancer (PC). However, it is not ideal to treat PC by inhibiting EZH2. This study reported that the combined use of pan-peroxisome proliferator-activated receptor (PPAR) agonist could significantly improve the anti-PC effect of EZH2 inhibitor. In vitro, PC cell lines PANC-1 and AsPC-1 were cultured, and MTT and flow cytometry were performed to observe the effects of pan-PPAR agonist bezafibrate and EZH2 selective inhibitor GSK126 on cell viability and apoptosis. In vivo, CDXs of PANC-1 and AsPC-1 were established to observe the effects of bezafibrate and GSK126 on bearing tumors. Western blotting was performed to detect the protein expressions of H3K27me3, β-catenin, p-β-catenin, cyclin D1, c-Myc, and cleaved caspase 3 in vitro and in vivo. The results showed that bezafibrate significantly improved the effects of GSK126 on proliferation inhibition and apoptosis promotion in vitro and the growth suppression of CDX tumors in vivo. It also significantly enhanced the effects of GSK126 on upregulating the expression level of p-β-catenin and that of cleaved caspase 3 in vitro and in vivo. In parallel, downregulation of the expression levels of H3K27me3, β-catenin, cyclin D1, and c-Myc was also observed in vitro or in vivo. These results suggest that the combination of bezafibrate and GSK126 has synergistic effects on PC, and the molecular mechanism may be related to the enhanced inhibition of the Wnt/β-catenin signaling pathway. We believe that targeting the EZH2-PPAR axis is a potential therapeutic pathway for PC.