Endogenous noncoding circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but their expression pattern in breast cancer has remained largely unknown. In this two-stage study, we first used an Arraystar Human circRNA Array to construct a genome-wide circRNA profile. We then selected candidate circRNAs for validation using a quantitative real-time polymerase chain reaction system. CircRNA/miRNA interactions were predicted and sequence analyses were performed. Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. These circRNAs targeted complementary miRNA response elements. The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.

Objective: To investigate suitable forecasting models for tuberculosis (TB) in a Chinese population by comparing the predictive value of the autoregressive integrated moving average (ARIMA) model and the ARIMA-generalized regression neural network (GRNN) hybrid model. Methods: We used the monthly incidence rate of TB in Lianyungang city from January 2007 through June 2016 to construct a fitting model, and we used the incidence rate from July 2016 to December 2016 to evaluate the forecasting accuracy. The root mean square error (RMSE), mean absolute percentage error (MAPE), mean absolute error (MAE) and mean error rate (MER) were used to assess the performance of these models in fitting and forecasting the incidence of TB. Results: The ARIMA (10, 1, 0) (0, 1, 1) 12 model was selected from plausible ARIMA models, and the optimal spread value of the ARIMA-GRNN hybrid model was 0.23. For the fitting dataset, the RMSE, MAPE, MAE and MER were 0.5594, 11.5000, 0.4202 and 0.1132, respectively, for the ARIMA (10, 1, 0) (0, 1, 1) 12 model, and 0.5259, 11.2181, 0.3992 and 0.1075, respectively, for the ARIMA-GRNN hybrid model. For the forecasting dataset, the RMSE, MAPE, MAE and MER were 0.2805, 8.8797, 0.2261 and 0.0851, respectively, for the ARIMA (10, 1, 0) (0, 1, 1) 12 model, and 0.2553, 5.7222, 0.1519 and 0.0571, respectively, for the ARIMA-GRNN hybrid model. Conclusions: The ARIMA-GRNN hybrid model was shown to be superior to the single ARIMA model in predicting the short-term TB incidence in the Chinese population, especially in fitting and forecasting the peak and trough incidence.

Background:Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by their aggressive nature and poor associated survival. MicroRNAs (miRs) have been found to play an important role in the occurrence and development of human cancers, but their role in the prognosis of TNBC patients remains unclear. We performed a meta-analysis to explore the prognostic value of miRs in TNBC.Methods:We systematically searched the PubMed, Embase, and Web of Science databases to identify eligible studies. A meta-analysis was performed to estimate the pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for the associations between levels of miR expression (predictive factors) and overall survival (OS) and disease-free survival (DFS) (outcomes) in patients with TNBC.Results:After performing the literature search and review, 21 relevant studies including 2510 subjects were identified. Six miRs (miR-155, miR-21, miR-27a/b, miR-374a/b, miR-210, and miR-454) were assessed in the meta-analysis. Decreased expression of miR-155 was associated with reduced OS (adjusted HR = 0.58, 95% CI: 0.34–0.99; crude HR = 0.67, 95% CI: 0.58–0.79). High miR-21 expression was also predictive of reduced OS (crude HR = 2.50, 95% CI: 1.56–4.01). We found that elevated levels of miR-27a/b, miR-210, and miR-454 expression were associated with shorter OS, while the levels of miR-454 and miR-374a/b expression were associated with DFS.Conclusions:Specific miRs could serve as potential prognostic biomarkers in TNBC. Due to the limited research available, the clinical application of these findings has yet to be verified.

BackgroundA variety of abnormalities in vitamin D metabolism have been reported in patients with active tuberculosis. However, intervention trials have produced inconsistent results. We hypothesized that genetic and epigenetic changes in the key genes of the vitamin D metabolic pathway may partly explain the differences between studies.MethodsWe performed a case-control study followed by a prospective cohort study. We recruited 122 patients with pulmonary tuberculosis and 118 healthy controls. The serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were measured. The methylation of the promoter regions of key genes in the vitamin D metabolic pathway (CYP24A1, CYP27A1, CYP27B1, CYP2R1, and VDR) was detected using the Illumina MiSeq platform. The specific methylation profiles were examined as epigenetic biomarkers. The sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to estimate the predictive value of the biomarkers.ResultsThe baseline serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations in the cases were significantly lower than those in the controls (51.60 ± 27.25 nmol/L vs. 117.50 ± 75.50 nmol/L, Z = − 8.515, P < 0.001; 82.63 ± 51.43 pmol/L vs. 94.02 ± 49.26 pmol/L, Z = − 2.165, P = 0.03). We sequenced 310 CpG sites in five candidate genes. After Bonferroni correction, there were 55 differentially methylated CpG sites between cases and controls; 41.5% were in the CYP27B1 gene, 31.7% were in the CYP24A1 gene, 14.7% were in the VDR gene, and 12.3% were in the CYP27A1 gene. When we designated the CpG sites that remained significant after the Bonferroni correction as the biomarkers, the area under the curve (AUC) for the cumulative methylation was 0.810 (95% CI 0.754–0.866). There was an interaction between CYP27A1 methylation level and 1,25-dihydroxyvitamin D concentration associated with the risk of TB (ORinteraction = 4.11, 95% CI 1.26–13.36, P = 0.019). The serum 1,25-dihydroxyvitamin D concentration at the end of the intensive treatment stage was related to a patient’s prognosis (P = 0.008). There were 23 CpG sites that were individually related to the treatment outcomes, but the relationships were not significant after the Bonferroni correction.ConclusionBoth serum vitamin D concentrations and the methylation levels of key genes in the vitamin D metabolic pathway are related to the risk and prognosis of tuberculosis.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0552-6) contains supplementary material, which is available to authorized users.

Background As a new class of endogenous ncRNAs, circRNAs have been recently verified to be involved in the carcinogenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a candidate circRNA (hsa_circ_0000337) in esophageal squamous cell carcinoma (ESCC). Patients and methods The altered expression of hsa_circ_0000337 was validated in clinical samples from 48 patients with ESCC. The human esophageal carcinoma cell lines KYSE-150 and TE-1, and the normal human esophageal epithelial cell line (HET-1A) were applied for functional analysis of hsa_circ_0000337. Cell proliferation was measured using the Cell Counting Kit-8 assay and the colony formation assay. Cell invasion and migration were detected by Transwell and wound healing assays, respectively. We further performed bioinformatic analysis and luciferase reporter assays to explore the role of hsa_circ_0000337 as a miRNA sponge. Results hsa_circ_0000337 was significantly upregulated in ESCC tissues compared to adjacent normal-appearing tissues ( P <0.0001). In our in vitro experiment, the expression of hsa_circ_0000337 was higher in TE-1 compared to the normal human esophageal epithelial cell line HET-1A ( P <0.001), but was not significantly different in KYSE-150 ( P >0.05). Knockdown of hsa_circ_0000337 significantly inhibited cell proliferation, migration, and invasion in TE-1 and KYSE-150 cell lines. Bioinformatics predicted and luciferase reporter assay verified that hsa_circ_0000337 could bind to miR-670-5p, a ncRNA involved in carcinogenesis. It is estimated that 21 genes are regulated by miR-670-5p. Conclusion hsa_circ_0000337 was found to be an upregulated circRNA that is related to ESCC and promotes the progression of disease by regulating cell proliferation, migration, and invasion. These findings suggest that this circRNA could be a promising diagnostic biomarker and potential therapeutic target.