Identification of GSN and LAMC2 as Key Prognostic Genes of Bladder Cancer by Integrated Bioinformatics Analysis.

Bladder cancer is a common malignancy with mechanisms of pathogenesis and progression. This study aimed to identify the prognostic hub genes, which are the central modulators to regulate the progression and proliferation in the specific subtype of bladder cancer. The identification of the candidate hub gene was performed by weighted gene co-expression network analysis to construct a free-scale gene co-expression network. The gene expression profile of GSE97768 from the Gene Expression Omnibus database was used. The association between prognosis and hub gene was evaluated by The Cancer Genome Atlas database. Four gene-expression modules were significantly related to bladder cancer disease: the red module (human adenocarcinoma lymph node metastasis), the darkturquioise module (grade 2 carcinoma), the lightgreen module (grade 3 carcinoma), and the royalblue module (transitional cell carcinoma lymphatic metastasis). Based on betweenness centrality and survival analysis, we identified laminin subunit gamma-2 (LAMC2) in the grade 2 carcinoma, gelsolin (GSN) in the grade 3 carcinoma, and homeodomain-interacting protein kinase 2 (HIPK2) in the transitional cell carcinoma lymphatic metastasis. Subsequently, the protein levels of LAMC2 and GSN were respectively down-regulated and up-regulated in tumor tissue with the Human Protein Atlas (HPA) database. Our results suggested that LAMC2 and GSN are the central modulators to transfer information in the specific subtype of the disease.

Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer.

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.

Indirect comparison of efficacy and safety between immune checkpoint inhibitors and antiangiogenic therapy in advanced non-small-cell lung cancer.

In this study, we conducted an indirect comparison analysis to compare the efficacy and safety of immune checkpoint inhibitors with those of antiangiogenic therapy-two effective treatment methods for advanced non-small-cell lung cancer (NSCLC). Eligible randomised control trials of immune checkpoint inhibitors, antiangiogenic therapy, and doublet platinum-based therapy published up to July 2017 were comprehensively analysed. Through the indirect comparison analysis of 37 trials involving 16810 patients, treatments were compared for overall survival (OS) and grade 3-5 adverse events. For first-line treatment, the use of pembrolizumab alone (hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.4-0.91) and a combination of bevacizumab and doublet platinum-based therapy (HR: 0.86; 95% CI: 0.75-0.99) demonstrated substantial survival benefits compared with doublet platinum-based therapy. For subsequent treatment, nivolumab may provide higher efficacy and lower toxicity than antiangiogenic therapy. Overall, anti-PD1 monoclonal antibodies may be superior to antiangiogenic therapy in terms of OS and grade 3-5 adverse events. This meta-analysis suggests that pembrolizumab and nivolumab might be favourable choices for first-line and subsequent treatment, respectively, for patients with advanced NSCLC. Additional randomised control trials are required for a comprehensive evaluation of the outcomes among regimens.

Effect of Long-term Incretin-Based Therapies on Ischemic Heart Diseases in Patients with Type 2 Diabetes Mellitus: A Network Meta-analysis.

Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up. The network meta-analysis was performed using R Software with a GeMTC package. A total of 40 trials were included. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 agonists were associated with a lower risk of myocardial infarction (MI) than were sulfonylureas (odds ratio [95% credible interval] 0.41 [0.24-0.71] and 0.48 [0.27-0.91], respectively). These results suggested that patients with T2DM receiving long-term incretin-based therapies have a lower risk of MI than do those receiving sulfonylurea-based therapy. These findings highlight the risks of cardiovascular events in patients who receive long-term incretin-based therapies, and may provide evidence for the selection of antidiabetic therapy in the future.