RESUMEN
Polybrominated diphenyl ethers (PBDEs) and their alternatives (e.g., dechlorane plus (DPs) and decabromodiphenyl ethane (DBDPE)) are ubiquitous in various environmental media. However, limited data is available on these chemicals in edible fish species from the wide-open South China Sea (SCS). In the present study, ten legacy PBDEs and three substitutions (DBDPE and two DPs) were analyzed in 16 wild fish species sampled from the open SCS to investigate their spatial and species-specific variations. The results showed that the total concentrations of PBDEs, DBDPE, and DPs in fish samples were in the range of 1.69-47.6, not detected (nd) to 21.0, and nd to 3.80 ng/g lipid weight (lw), respectively. BDEs 47, 209 and 100 were the dominant target PBDE congeners, representing 49.2%, 17.2% and 9.93% of the total PBDE concentrations, respectively. Higher concentrations of PBDEs, DBDPE, and DPs were found in ï¬sh species from the Wanshan Archipelago compared to those from the Mischief Reef and the Yongxing Island, suggesting the significant influence of anthropogenic activities. Species-specific differences in levels of PBDEs were observed, with the order of bathydemersal > demersal > pelagic ≈ reef-associated > benthopelagic species. The average fanti value of all fish samples was 0.68, suggesting commercial DP products as a contamination source. The levels of PBDEs, DPs, and DBDPE in fish samples were relatively low compared with those from other locations around the globe. Finally, the health risks concerning the ingestion of BDEs 47, 99, 153 and 209 via ï¬sh consumption collected from the SCS are negligible.
RESUMEN
Cholangiocarcinoma (CCA) is a type of malignant tumor that originates in the mucosal epithelial cells of the biliary system. It is a highly aggressive cancer that progresses rapidly, has low surgical resection rates and a high recurrence. At present, no prognostic molecular biomarker for CCA has been identified. However, CCA progression is affected by mRNA precursors that modify gene expression levels and protein structures through alternative splicing (AS) events, which create molecular indicators that may potentially be used to predict CCA outcomes. The present study aimed to construct a model to predict CCA prognosis based on AS events. Using prognostic data available from The Cancer Genome Atlas, including the percent spliced index of AS events obtained from TCGASpliceSeq in 32 CCA cases, univariate and multivariate Cox regression analyses were performed to assess the associations between AS events and the overall survival (OS) rates of patients with CCA. Additional multivariate Cox regression analyses were used to identify AS events that were significantly associated with prognosis, which were used to construct a prediction model with a prognostic index (PI). A receiver operating characteristic (ROC) curve was used to determine the predictive value of the PI, and Pearson's correlation analysis was used to determine the association between OS-related AS events and splicing factors. A total of 38,804 AS events were identified in 9,673 CCA genes, among which univariate Cox regression analysis identified 1,639 AS events associated with OS (P<0.05); multivariate Cox regression analysis narrowed this list to 23 CCA AS events (P<0.001). The final PI model was constructed to predict the survival of patients with CCA; the ROC curve demonstrated that it had a high predictive power for CCA prognosis, with a highest area under the curve of 0.986. Correlations between 23 OS-related AS events and splicing factors were also noted, and may thus, these AS events may be used to improve predictions of OS. In conclusion, AS events exhibited potential for predicting the prognosis of patients with CCA, and thus, the effects of AS events in CCA required further examination.
RESUMEN
MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR1323p and CCA remains unknown. In the present study, the clinical role of miR1323p and its potential signaling pathways were investigated by multiple approaches. Reverse transcriptionquantitative PCR (RTqPCR), CCAassociated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNAmicroarray or miRNAsequencing data were screened, and metaanalyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR1323p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNAsequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Proteinprotein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and nontumor biliary epithelium. The metaanalyses comprised 10 groups of RTqPCR data, eight GEO microarray datasets and one TCGA miRNAsequencing dataset. The SMD of miR1323p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR1323p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR1323p in the early stage of CCA (stages III) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages IIIIVB), 7.3034±0.3267 (P=0.003). Consistently, the miR1323p level in lowgrade CCA (grades G1G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with highgrade CCA (grades G3G4) (P=0.037). Furthermore, 555 potential target genes of miR1323p in CCA were mainly enriched in the 'Focal AdhesionPI3KAktmTORsignaling pathway'. In conclusion, upregulation of miR1323p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.