Diffuse large B-cell lymphoma (DLBCL) ranks among the most prevalent malignancies of the lymphohematopoietic system in adults. The PRSS (Serine Protease) protein family members had been reported to be involved in carcinogenesis as well as tumor progression. Here, we aimed to explore the expression profile of PRSS3 in DLBCL and investigate its clinical significance as well as detailed functions. We retrospectively enrolled 155 DLBCL patients from our hospital and tested protein expression level of PRSS3 through immunohistochemical staining. Accordingly, PRSS3 was highly expressed in certain DLBCL tissues. Chi-square test revealed that higher PRSS3 expression was correlated with advanced Ann Arbor stage, elevated serum LDH level, and higher International Prognostic Index. Moreover, univariate and multivariate analyses confirmed that higher PRSS3 can act as an independent unfavorable prognostic predictor for DLBCL. Two human DLBCL cell lines, SUDHL10 and OCI-LY3, were subjected for knockdown assays, followed by phonotype tests including proliferation and invasion. According to the cellular experiments, PRSS3-knockdown resulted in impaired DLBCL proliferation in the two cell lines above. Taken together, PRSS3 is a novel prognostic factor for DLBCL, which functions by multiple signaling pathways.

Background The mechanism through which death-associated protein kinase 1 (DAPK1) causes hepatocellular carcinoma (HCC) progression remains unclear. In this study, we aimed to identify key proteins that were altered after DAPK1 knockout. Methods Stable DAPK1 knockout HCC cell lines were established, then the differentially expressed genes (DEGs) of HCC were screened using the NetworkAnalyst database and enriched using the Metascape software. Protein-protein interaction networks (PPIs) were analyzed and visualized using the STRING database expansion. Results In total, 732 differentially expressed genes were identified, including 415 upregulated genes and 317 downregulated genes. Through Cytoscape software scoring, 10 pivotal genes were found to be closely related to changes in DAPK1 expression; Kininogen-1 (KNG1), Complement C3 (C3), Metalloproteinase inhibitor 1 (TIMP1), and Alpha-2-HS-glycoprotein (AHSG) were the most strongly associated with DAPK1 expression changes. Moreover, western blot analysis results revealed that changes in the levels of proteins encoded by the four key genes after DAPK1 knockout were consistent with those seen in the database screening. Conclusions These results provide a direction for further studies on the DAPK1 gene and on the mechanism through which DAPK1 leads to hepatocellular carcinoma development.

BackgroundSarcoidosis is an inflammatory disease characterized by non-caseating granuloma formation in various organs, with several recognized genetic and environmental risk factors. Despite substantial progress, the genetic determinants associated with its prognosis remain largely unknown.ObjectivesThis study aimed to identify the genetic changes involved in sarcoidosis and evaluate their clinical relevance.MethodsWe performed whole-exome sequencing (WES) in 116 sporadic sarcoidosis patients (acute sarcoidosis patients, n=58; chronic sarcoidosis patients, n=58). In addition, 208 healthy controls were selected from 1000 G East Asian population data. To identify genes enriched in sarcoidosis, Fisher exact tests were performed. The identified genes were included for further pathway analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, we used the STRING database to construct a protein network of rare variants and Cytoscape to identify hub genes of signaling pathways.ResultsWES and Fisher’s exact test identified 1,311 variants in 439 protein-coding genes. A total of 135 single nucleotide polymorphisms (SNPs) on 30 protein-coding genes involved in the immunological process based on the GO and KEGG enrichment analysis. Pathway enrichment analysis showed osteoclast differentiation and cytokine–cytokine receptor interactions. Three missense mutations (rs76740888, rs149664918, and rs78251590) in two genes (PRSS3 and CNN2) of immune-related genes showed significantly different mutation frequencies between the disease group and healthy controls. The correlation of genetic abnormalities with clinical outcomes using multivariate analysis of the clinical features and mutation loci showed that the missense variant (rs76740888, Chr9:33796673 G>A) of PRSS3 [p=0.04, odds ratio (OR) = 2.49] was significantly associated with chronic disease prognosis. Additionally, the top two hub genes were CCL4 and CXCR4 based on protein–protein interaction (PPI) network analysis.ConclusionOur study provides new insights into the molecular pathogenesis of sarcoidosis and identifies novel genetic alterations in this disease, especially PRSS3, which may be promising targets for future therapeutic strategies for chronic sarcoidosis.