ABSTRACT
Background: Bladder cancer (BLCA) is a common malignancy from urinary tract. Although the diagnosis and treatment of bladder cancer has made great progress in the past few decades, the effects of existing treatment methods are still limited. Therefore, it is still necessary to develop new methods to assist in the disease management and treatment. Tumor antigens are tumor-specific surface molecules and are generally considered to be the main components of a typical cancer vaccine, which could initiate and active immune cells to recognize and eliminate cancer cells. In the context of the COVID-19 pandemic, mRNA vaccines have re-entered people's vision. Methods: The genomic and clinical data of 411 BLCA and 19 normal tissues were acquired from The Cancer Genome Atlas (TCGA) and GSE13507 cohorts. Differential expression genes and mutation analysis were performed to screen out potential antigens, Kaplan-Meier curves were carried out to investigate the correlation between the level of potential antigens and OS of patients. Immuno-phenotyping of 411 tumor samples was based on the single-sample gene sets enrichment analysis (ssGSEA). The tumor immune microenvironment characteristics was explored in each immune subtype. Weighted gene co-expression network analysis (WGCNA) was used to clusterimmune-related genes and screen the hub genes, and pathway enrichment analyses were performed on the hub modules related to immune subtypes in the WGCNA.Results: Through genetic and transcriptional analysis on TCGA and GSE13507 datasets, we have identified 6 genes as potential candidate genes for BLCA specific tumor antigens. We also identified 3 immune subtypes of BLCA, which displayed distinct clinical, molecular and immune-related characteristics. In addition, we have constructed immune landscape to identify the immune cell components of each BLCA patient, which could predict clinical outcome of the patients, and assist in the development of personalized mRNA vaccines. Conclusions: our findings indicated that 6 genes such as PTPN6 may be potential tumor antigens, and provide a reliable reference for the further development and management of cancer vaccines.
Subject(s)
COVID-19ABSTRACT
Background No clinically proven effective antiviral strategy exists for the epidemic Coronavirus Disease 2019 (COVID-19). Methods We conducted a prospective, randomized, controlled, open-label multicenter trial involving adult patients with COVID-19. Patients were randomly assigned in a 1:1 ratio to receive conventional therapy plus Umifenovir (Arbidol) (200mg*3/day) or Favipiravir (1600mg*2/first day followed by 600mg*2/day) for 10 days. The primary outcome was clinical recovery rate of Day 7. Latency to relief for pyrexia and cough, the rate of auxiliary oxygen therapy (AOT) or noninvasive mechanical ventilation (NMV) were the secondary outcomes. Safety data were collected for 17 days. Results 240 enrolled COVID-19 patients underwent randomization; 120 patients were assigned to receive Favipiravir (116 assessed), and 120 to receive Arbidol (120 assessed). Clinical recovery rate of Day 7 does not significantly differ between Favipiravir group (71/116) and Arbidol group (62/120) (P=0.1396, difference of recovery rate: 0.0954; 95% CI: -0.0305 to 0.2213). Favipiravir led to shorter latencies to relief for both pyrexia (difference: 1.70 days, P<0.0001) and cough (difference: 1.75 days, P<0.0001). No difference was observed of AOT or NMV rate (both P>0.05). The most frequently observed Favipiravir-associated adverse event was raised serum uric acid (16/116, OR: 5.52, P=0.0014). Conclusions Among patients with COVID-19, Favipiravir, compared to Arbidol, did not significantly improve the clinically recovery rate at Day 7. Favipiravir significantly improved the latency to relief for pyrexia and cough. Adverse effects caused Favipiravir are mild and manageable. This trial is registered with Chictr.org.cn (ChiCTR2000030254).