Circular RNAs (circRNAs) are regarded as a novel class of widespread endogenous non-coding RNAs, which may play important roles in tumorigenesis by regulating gene expression. Nevertheless, the characterization of circRNAs in epithelial ovarian cancer (EOC) remains largely unknown. This study aimed to investigate circRNA expression profiles in EOC. A total of 54 EOC specimens and 54 normal ovarian tissues (controls) were collected. circRNA-sequencing based circRNA expression profiles were identified in 4 EOC specimens and compared with 4 normal ovarian tissues. circRNA-sequencing data were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in the 54 EOC specimens and 54 normal ovarian tissues. The association between differentially expressed circRNAs and various clinicopathological features of EOC was determined using a non-parametric test. Univariate analysis was performed using the log-rank test. A total of 4,388 circRNAs (2,556 up-and 1,832 downregulated; fold change of ≥2 and P<0.05) were identified to be differentially expressed in the EOC specimens compared with the normal ovarian tissues. Of these, the levels of 6 circRNAs (circBNC2, circEXOC6B, circFAM13B, circ-N4BP2L2, circRHOBTB3 and circCELSR1) were confirmed by RT-qPCR. Our data further indicated that these 6 circRNAs were associated with various clinicopathological features of EOC. More importantly, we found that circEXOC6B and circ-N4BP2L2 may act as novel prognostic biomarkers in patients with EOC. On the whole, the results of this study indicate that differentially expressed circRNAs may participate in the pathogenesis of EOC and may thus have potential for use as novel diagnostic and prognostic biomarkers for EOC. Future experiments with larger sample sizes are required to verify the current findings and illuminate the regulatory mechanisms of action of circRNAs in the tumorigenesis of EOC.
PurposeTo investigate the association of cancer stem-cell markers [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), and Nanog homebox (NANOG)] expression with clinicopathological properties and overall survival (OS) in operative rectal cancer (RC) patients receiving adjuvant therapy.Materials and Methods153 patients with primary RC receiving surgery were enrolled. Tumor tissue and paired adjacent normal tissue sample were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunofluorescent staining. The median follow-up duration was 5.2 years, and the last follow-up date was August 2016.ResultsTumor tissue OCT4 (p<0.001), SOX2 (p=0.003), and NANOG (p<0.001) expressions were higher than those in adjacent tissue. OCT4 expression was positively correlated with pathological grade (R=0.185, p=0.022), tumor size (R=0.224, p=0.005), and N stage (R=0.170, p=0.036). NANOG expression was positively associated with tumor size (R=0.169, p=0.036). Kaplan-Meier suggested that OCT4+ was associated with worse OS compared with OCT4− (p<0.001), while no association of SOX2 (p=0.121) and NANOG expressions (p=0.195) with OS was uncovered. Compared with one or no positive marker, at least two positive markers were associated with shorter OS (p<0.001), while all three positive markers were correlated with worse OS compared with two or less positive markers (p<0.001). Multivariate Cox's analysis revealed that OCT4+ (p<0.001) and N stage (p=0.046) were independent factors for shorter OS.ConclusionTumor tissue OCT4 expression was correlated with poor differentiation, tumor size, and N stage, and it can serve as an independent prognostic biomarker in operative patients with RC receiving adjuvant therapy.
Previous studies investigating the association between statin use and survival outcomes in gynecologic cancers have yielded controversial results. We conducted a systematic review and meta-analysis to evaluate the association based on available evidence. We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and PubMed from inception to January 2017. Studies that evaluated the association between statin use and survival outcomes in gynecologic cancers were included. Pooled hazard ratios (HRs) for overall survival, disease-specific survival and progression-free survival were calculated using a fixed-effects model. A total of 11 studies involving more than 6,920 patients with endocrine-related gynecologic cancers were identified. In a meta-analysis of 7 studies involving 5,449 patients with endocrine-related gynecologic cancers, statin use was linked to improved overall survival (HR, 0.71; 95% confidence interval [CI], 0.63 to 0.80) without significant heterogeneity (I2 = 33.3%). Statin users also had improved disease-specific survival (3 studies, HR, 0.72; 95% CI, 0.58 to 0.90, I2 = 35.1%) and progression-free survival (3 studies, HR, 0.68; 95% CI, 0.49 to 0.93, I2 = 33.6%) in endocrine-related gynecologic cancers. Our findings support that statin use has potential survival benefits for patients with endocrine-related gynecologic cancers. Further large-scale prospective studies are required to validate our findings.
Previous studies evaluating the association between smoking and risk of cholangiocarcinoma (CCA) have yielded controversial results. We conducted a meta-analysis to evaluate the association based on available evidence. We searched the databases of Embase, PubMed and Cochrane Central Register of Controlled Trials from inception to April 11, 2017. Studies that investigated the association between smoking and risk of CCA were included. Pooled odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated using either a random-effects or a fixed-effects model. A total of 22 studies involving 324,333 participants were identified. The summary OR of CCA was 1.31 (95% CI, 1.15 to 1.51) for smokers versus nonsmokers. The increased risk was independent of diabetes mellitus, bilious tract stone disease, and liver cirrhosis. Smokers also had increased risk of intrahepatic CCA (12 studies; OR, 1.31; 95% CI, 1.06 to 1.63) and extrahepatic CCA (12 studies; OR, 1.32; 95% CI, 1.10 to 1.59) compared with nonsmokers. The results of our meta-analysis support the hypothesis that there is a moderate association between cigarette smoking and risk of CCA.
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