[Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients].

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

[Expression and Regulatory Mechanism of Autophagy-related Genes in Synovial Tissues of Patients with Rheumatoid Arthritis].

Objective To investigate the expression regulation of autophagy-related genes(ATG)and the mechanism of autophagy in rheumatoid arthritis(RA).Methods The differentially expressed genes(DEG)of RA were identified from GSE55235 and GSE55457,on the basis of which the differentially expressed autophagy-related genes(DE-ATG)were selected from the Human Autophagy Database.STRING 11.0 and GeneMANIA were used to establish protein-protein interaction networks.Further,the transcription factor-gene-miRNA co-expression network was established via NetworkAnalyst and Cytoscape.Finally,receiver operating characteristic(ROC)curve and DrugBank were employed to evaluate the efficacy of the predicted biomarkers and the performance of drugs targeting DE-ATG.GraphPad Prism 8.2.1 and R 4.0.3 were used for statistical analysis and graphics.Results A total of 485 DEG were enriched in signaling pathways such as T cell activation,hormone regulation,osteoclast differentiation,RA,and chemokines.Eleven DE-ATG regulated the expression of RUNX1,TP53,SOX2,and hsa-mir-155-5p in synovial tissues of RA patients and were involved in the response to environmental factors such as 2,3,7,8-tetrachlorodibenzodioxin and silicon dioxide.The ROC curve analysis identified the DE-ATG with good sensitivity and specificity,such as MYC,MAPK8,CDKN1A,and TNFSF10,which can be used to distinguish certain phenotypes and serve as novel biomarkers for RA.Conclusions In RA,down-regulated DE-ATG expression may promote apoptosis and lysis of chondrocytes.The identified novel biomarkers provides new ideas and methods for diagnosing and treating RA.The establishment of transcription factor-miRNA-gene co-expression network provides direct evidence for dissecting synovial inflammation and articular cartilage destruction.

[Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients].

Objective To investigate the expression of thioredoxin reductase 3(TXNRD3),a selenoprotein,in 33 human malignant tumors and then analyze its effect on the survival prognosis.Methods We employed the genotype-tissue expression project database,the cancer cell line encyclopedia,and the cancer genome atlas to explore the expression of TXNRD3 gene in 33 human malignant tumors and analyze its impact on the survival prognosis.Further,we explored the correlations of TXNRD3 with immune cells and immune infiltration in the tumor microenvironment,as well as with neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.Subsequently,human samples were classified into high-and low-expression groups according to TXNRD3 gene expression levels,and the enrichment analysis of biological functions and signaling pathways was performed.Results The analysis with multiple databases showed that TXNRD3 was highly expressed in 15 tumors.The survival analysis showed that TXNRD3 was significantly associated with poor prognosis in pancreatic cancer patients.In addition,the expression level of TXNRD3 was correlated with immune infiltration in tumor microenvironment,neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.TXNRD3 affected the expression of DNA mismatch repair genes.The gene set enrichment indicated that TXNRD3 was involved in regulating multiple signaling pathways associated with tumor metabolism and tumor immunity.Conclusion TXNRD3 is widely expressed in tumors and has a clinical value for the survival prognosis prediction and treatment of multiple tumors,demonstrating the potential of being a promising biomarker for targeted treatment of multiple tumors.