关键词: 泛素样含植物同源结构域和环指结构域蛋白1;软组织肉瘤;临床特征;共表达基因;差异表达基因;分子功能

Abstract: Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1) gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas (TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyzed differentially expressed genes (DEGs) and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type (liposarcoma 22.2%,synovial sarcoma 3.8%,leiomyosarcoma 40.7%,malignant peripheral nerve sheath tumor 3.8%,myxofibrosarcoma 9.6%,pleomorphic sarcoma 19.9%,P＝0.001),tumor necrosis (none 38.8%,focal necrosis 20.8%,moderate necrosis 33.8%,extensive necrosis 6.6%,P＝0.010),and tumor metastasis (no metastasis 67%,metastasis 33%,P＜0.001).In different clinical subgroups (age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival (OS),disease-specific survival (DSS),and progression-free interval (PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3029 DEGs of UHRF1 in STS were obtained with a threshold of |log2 fold-change (FC)| > 1.0 and adjusted P value < 0.05,in which 1 228 genes were up-regulated and 1801 genes were down-regulated;GO enrichment analyed primary biological processes (BP),original cellular components (CC),and original molecular functions (MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of |log2 fold-change (FC)| > 2.0 and adjusted P value < 0.05.The top 10 hub genes were analyzed. The top 3 hub genes were GCG, SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Key words: ubiquitin-like containing PHD and RING finger domains 1;soft tissue sarcoma;clinical characteristics;co-expressed genes;differentially expressed genes;molecular function