No abstract

Background: Diffuse lower-grade gliomas (LGGs) are infiltrative and heterogeneous neoplasms. Gene signature including multiple protein-coding genes (PCGs) is widely used as a tumor marker. This study aimed to construct a multi-PCG signature to predict survival for LGG patients.Methods: LGG data including PCG expression profiles and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Survival analysis, receiver operating characteristic (ROC) analysis, and random survival forest algorithm (RSFVH) were used to identify the prognostic PCG signature.Results: From the training (n = 524) and test (n = 431) datasets, a five-PCG signature which can classify LGG patients into low- or high-risk group with a significantly different overall survival (log rank P < 0.001) was screened out and validated. In terms of prognosis predictive performance, the five-PCG signature is stronger than other clinical variables and IDH mutation status. Moreover, the five-PCG signature could further divide radiotherapy patients into two different risk groups. GO and KEGG analysis found that PCGs in the prognostic five-PCG signature were mainly enriched in cell cycle, apoptosis, DNA replication pathways.Conclusions: The new five-PCG signature is a reliable prognostic marker for LGG patients and has a good prospect in clinical application.

Background: Research has shown that the progression of clear cell renal cell carcinoma (ccRCC) is modulated by long non-coding RNAs (lncRNAs). However, the roles of specific lncRNAs in the malignancy of ccRCC are still unknown.Methods: TCGA and GSE66272 datasets were used to predict differentially expressed genes (DEGs) in ccRCC. ENCORI database was employed to display BIRC5 miRNA network and potential lncRNA interactions for miRNAs. KM plotter and correlation analyses were performed to identify the overall survival (OS)-and BIRC5-related miRNAs. Quantitative real-time PCR (qRT-PCR) was used to verify the BIRC5 mRNA in the seventy paired clinical samples of ccRCC tissues. The ccRCC A498 and 786-O were individually transfected with lncRNA SNHG3 and LINC00997 and then western blotting was used to detect the BIRC5 protein expression. The Dual-luciferase reporter assay was used to examine the regulatory interaction between lncRNA SNHG3 and microRNA (miRNA/miR)-10b-5p.Results: BICR5 is associated with the progression of ccRCC. The two novel lncRNAs (LINC00997, SNHG3) were up-regulated in ccRCC tissues and positively with the BICR5 protein expression. However, Suppressing SNHG3 expression reduced BIRC5 protein expression compared with the LINC00997, most importantly, Suppressing SNHG3 expression suppressed tumor progression in vitro. In addition, SNHG3 promotes the expression of BIRC5 protein by sponging microRNA-10b-5p.Conclusions: Our findings suggest that SNHG3 plays a vital role in promoting ccRCC via the microRNA-10b-5p/BIRC5 axis and may serve as a novel therapeutic target for the treatment of patients with ccRCC.

Relugolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, has been well studied in the treatment of endometriosis symptomatic. It is mainly metabolized by the CYP3A subfamily of P450 enzymes, while minorly metabolized by CYP2C8. Daidzein in different dose groups exhibited a certain induction on the mRNA expression level of CYP3A4 and resulted in the potent induction of CYP3A4. However, it is still unknown whether daidzein and relugolix interact. We developed an effective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to study the effect of daidzein on the pharmacokinetics of relugolix in rats after oral administration of 12 mg/kg relugolix in a single or mixed of 50 mg/kg daidzein. The results showed that the method had respectable linearity (r2 > 0.999) on the scale of 0.7–1000 ng/mL. The intra-day precision was between 3.0% and 8.4% in this assay, and the inter-day was between 4.0% and 11.7%. The intra-day accuracy was from -4.3% to 6.1%, and the inter-day was 2.9% to 12.1%. Another three key indicators, including the stability, the recovery rate of extraction and the new technique’s matrix effect, were perfectly in accord with the test verification rule in the biological medium by the United States Food and Drug Administration. Meanwhile, treatment with daidzein led to a decrease in Cmax and AUC0–t of relugolix by about 15.56% and 21.36%, respectively. Although there was no statistical difference in pharmacokinetic parameters, it reflected the induction trend of daidzein on relugolix metabolism for food-drug interaction. It would provide reference and improvement value for subsequent experiments.

Background: Diffuse lower-grade gliomas (LGGs) are infiltrative and heterogeneous neoplasms. Gene signature including multiple protein coding genes (PCGs) is widely used as tumor markers. This study aimed to construct a multi-PCG signature to predict survival for LGG patients.Methods: LGG data including PCG expression profiles and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Survival analysis, receiver operating characteristic (ROC) analysis and random survival forest algorithm (RSFVH) were used to identify the prognostic PCG signature.Results: From the training (n = 524) and test (n = 431) datasets, a five-PCG signature which can classify LGG patients into low- or high-risk group with significantly different overall survival (Log Rank P < 0.001) was screened out and validated. In terms of prognosis predictive performance, the five-PCG signature is stronger than other clinical variables and IDH mutation status. Moreover, the five-PCG signature could further divide radiotherapy patients into two different risk groups. GO and KEGG analysis found PCGs in the prognostic five-PCG signature were mainly enriched in cell cycle, apoptosis, DNA replication pathways.Conclusions: The new five-PCG signature is a reliable prognostic marker with radiotherapy guidance significance for LGG patients and has a good prospect in clinical application.

Bladder cancer (BC) is a worldwide disease that affects a large number of people. This study analyzes the sensitivity and specificity of adenomatous polyposis coli (APC) methylation for BC detection in urine and tissues. Combining search results from PubMed and Embase, 20 studies were included. In tissue subgroups, the OR was 6.88 (95% confidence interval (CI 2.49–19.03, P<0.001), respectively. From urine studies, the pooled OR was 4.73 at a 5% significance level (95% CI 0.87-25.66, P<0.001). In addition, analysis of the interaction between APC methylation and BC showed strong association in the whole data set. From this study, the results suggest that APC promoter methylation may be the potential testing for BC diagnosis and provide a new viewpoint in the treatment of BC.

Purpose: To evaluate the effect of miR-378a/FSCN1 axis on tumor stemness and aerobic glycolysis in colorectal cancer cells (CRC). Methods: Abnormal expressions of miR-378a and FSCN1 in CRC tissues were analyzed through TCGA database. Cell viability and apoptosis were determined using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay and flow cytometry, respectively, while expression of miR-378a was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, Western blotting assay was used to assess protein expressions. The miR-378a target was evaluated using ENCORI and confirmed by luciferase assay. Aerobic glycolysis was evaluated by determining glucose uptake, lactate production and lactate dehydrogenase (LDH) activity. Results: Downregulation of miR-378a and upregulation of FSCN1 were observed in both CRC tissues and cell lines (p < 0.05). Overexpression of miR-378a and repression of FSCN1 reduced cell viability and tumor sphere formation, and induced cell apoptosis. Protein expression of SOX2, KLF4, Bmi1 and Oct-4 were downregulated by either the overexpression of miR-378a or repression of FSCN1 (p < 0.01). Glucose uptake, lactate production and LDH activity were inhibited by either overexpression of miR-378a or repression of FSCN1, while cytotoxicity of Dox and 5-Fu was increased by upregulation of miR-378a or downregulation of FSCN1 (p < 0.05). The predictive results of ENCORI demonstrated that FSCN1 was the direct target of miR-378a, and this was confirmed by luciferase assay results (p < 0.005). All the effects of miR-378a in CRC were reversed by overexpression of FSCN1 (p < 0.05). Conclusion: This study has shown that miR-378a suppresses tumor stemness and increases the cytotoxicity of chemotherapeutic drugs by directly targeting FSCN1, resulting in the prevention of CRC tumorigenesis. Thus, these findings suggest a new approach to the chemotherapeutic management of CRC.