Functional Significance of Cardiac Rehabilitation-Regulated Expression of Circulating MicroRNA-423-5p in Hypertensive Patients with Heart Failure with a Moderately Reduced Ejection Fraction.

BACKGROUND: Hypertension is a vital risk factor for heart failure, while cardiac rehabilita-tion can effectively improve cardiac function of heart failure patients. This study aimed to determine the impact of cardiac rehabilitation on microRNA-423-5p in hypertensive patients with heart failure with a moderately reduced ejection fraction. METHODS: Sixty hypertensive patients with heart failure with a moderately reduced ejec-tion fraction were randomly divided into cardiac rehabilitation group and positive control group with 30 cases per group, while 30 hypertensive patients without heart failure were recruited as negative control group. The cardiac rehabilitation group and positive control group were treated with 1-month cardiac rehabilitation combined with the routine treat-ment and routine treatment only, respectively. The New York Heart Association classi-fication, 6-minute walking test, and color Doppler echocardiography were adopted to detect cardiac function. Meanwhile, the expression of microRNA-423-5p and N-terminal pro-B-type natriuretic peptide was determined via Real-Time Fluorescence Quantitative PCR and electrochemiluminescence immunoassay. The diagnostic potential of microR- 423-5p and N-terminal pro-B-type natriuretic peptide was assessed by ROC curve analy- sis and multivariate linear regression model. RESULTS: Patients in cardiac rehabilitation group displayed significantly lower expression of microR-423-5p and better results of New York Heart Association classification, 6-min-ute walking test, and color Doppler echocardiography than those in positive controlgroup (P < .05). ROC analysis showed that microR-423-5p (AUC = 0.785; 95% CI: 0.686- 0.865; sensitivity = 73.33%; specificity = 73.33%) had better specificity and accuracy thanN-terminal pro-B-type natriuretic peptide (AUC=0.721; 95% CI: 0.617-0.811; sensitiv- ity = 81.67%; specificity = 63.33%). CONCLUSION: MicroR-423-5p was implicated in left ventricular hypertrophy and might be a potential biomarker for assessing the therapeutic effect of cardiac rehabilitation on hypertensive patients with heart failure with a moderately reduced ejection fraction.

Comprehensive analysis of prognostic genes in gastric cancer.

BACKGROUND: Gastric cancer is associated with high mortality, and effective methods for predicting prognosis are lacking. We aimed to identify potential prognostic markers associated with the development of gastric cancer through bioinformatic analyses. METHODS: Gastric cancer-associated gene expression profiles were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The key genes involved in the development of gastric cancer were obtained by differential expression analysis, coexpression analysis, and short time-series expression miner (STEM) analysis. The potential prognostic value of differentially expressed genes was further evaluated using a Cox regression model and risk scores. Hierarchical clustering was applied to validate the impact of key genes on the overall survival of gastric cancer patients. RESULTS: A total of 1381 genes were consistently dysregulated in the development of gastric cancer. Among them, 186 genes affected the overall survival of gastric cancer patients. The following genes had areas under the receiver operating characteristic curve greater than 0.9 in both datasets and were therefore considered key genes: ADAM12, CEP55, LRFN4, INHBA, ADH1B, DPT, FAM107A, and LOC100506388. LRFN4, DPT, and LOC100506388 were identified as potential prognostic genes for gastric cancer through a nomogram. Overexpression of LRFN4 and LOC100506388 was associated with a higher risk of gastric cancer. Finally, we found that tumors were infiltrated with high levels of Th2 cells and mast cells, and the infiltration levels were associated with overall survival in gastric cancer patients. CONCLUSIONS: We found that key dysregulated genes may have a prognostic value for the development of gastric cancer.

Comprehensive Identification of Bridge Genes to Explain the Progression from Chronic Hepatitis B Virus Infection to Hepatocellular Carcinoma.

BACKGROUND: Hepatitis B virus infection co-occurs in 33% of individuals with hepatocellular carcinoma worldwide. However, the molecular link between hepatitis B virus and hepatocellular carcinoma is unknown. Thus, we aimed to elucidate molecular linkages underlying pathogenesis through in-depth data mining analysis. MATERIALS AND METHODS: Differentially expressed genes were identified from patients with chronic hepatitis B virus infection, hepatocellular carcinoma, or both. Gene set enrichment analysis revealed signaling pathways involving differentially expressed genes. Protein-protein interaction networks, protein crosstalk, and enrichment were analyzed to determine whether differentially expressed gene products might serve as a bridge from hepatitis B virus infection to hepatocellular carcinoma pathogenesis. Prognostic potential and transcriptional and post-transcriptional regulators of bridge genes were also examined. RESULTS: We identified vital bridge factors in hepatitis B virus infection-associated hepatocellular carcinoma. Differentially expressed genes were clustered into modules based on relative protein function. Signaling pathways associated with cancer, inflammation, immune system, and microenvironment showed significant crosstalk between modules. Thirty-two genes were dysregulated in hepatitis B virus infection-mediated hepatocellular carcinoma. CPEB3, RAB26, SLCO1B1, ST3GAL6 and XK had higher connectivity in the modular network, suggesting significant associations with survival. CDC20 and NUP107 were identified as driver genes as well as markers of poor prognosis. CONCLUSION: Our results suggest that the sustained inflammatory environment created by hepatitis B virus infection is a risk factor for hepatocellular carcinoma. The identification of hepatitis B virus infection-related hepatocellular carcinoma bridge genes provides testable hypotheses about the pathogenesis of hepatocellular carcinoma.

GSTM1 and GSTT1 Gene Polymorphisms, Gene-Gene Interaction, and Esophageal Carcinoma Risk: Evidence from an Updated Meta-Analysis.

BACKGROUND: Published data regarding the association between GSTM1 and/or GSTT1 gene polymorphisms and esophageal cancer (EC) susceptibility remain inconclusive. To clarify these associations, a meta-analysis was conducted. METHODS: We conducted a comprehensive search in PubMed, Embase, and the China National Knowledge Infrastructure (CNKI) for all such manuscripts published as of May 1, 2017. The pooled odds ratio (ORs) with confidence intervals (95% CI) were estimated for each study to assess the strength of the association. A subgroup analysis, a sensitivity analysis, and a publication bias analysis were also performed. RESULTS: Data from 41 studies comprising 5291 EC cases and 8191 controls were available for analysis of the GSTM1 polymorphism, and data from 31 studies comprising 4330 EC cases and 6558 controls were available for analysis of the GSTT1 polymorphism. Analyses of the GSTM1 polymorphisms demonstrated that there was a significantly increased EC risk in GSTM1 null genotype carriers (OR = 1.319, 95% CI = 1.125-1.546, p for heterogeneity <0.001). In subgroup analyses by ethnicity, and categories of EC, a significantly increased EC risk was found in Asians (OR = 1.457, 95% CI = 1.212-1.751, p for heterogeneity <0.001) and patients whose histological type was unknown. Analyses of the GSTT1 polymorphisms indicated a positive correlation between the GSTT1 null genotype and the EC risk (OR = 1.233, 95% CI = 1.044-1.455, p for heterogeneity <0.001). In subgroup analyses stratified by ethnicity and categories of EC, similar statistical associations were observed in Asians, esophageal squamous cell carcinoma (ESCC) patients, and ESCC on Asian population. In the GSTM1-GSTT1 interaction analysis, we discovered remarkably enhanced EC risk for patients with the GSTM1 and GSTT1 dual null genotypes (OR = 1.962, 95% CI = 1.178-3.268, p for heterogeneity <0.001) compared with the reference GSTM1 and GSTT1 dual positive genotype. CONCLUSIONS: We conclude that the GSTM1 and GSTT1 null genotypes are associated with increased genetic susceptibility to EC in the overall human population, particularly among Asians. In addition, our findings suggest that persons with a null genotype for both the GSTM1 and GSTT1 genes are at higher risk of developing EC. Further well-designed studies are needed to confirm these associations.