The hepsin gene encodes a type II transmembrane serine protease. Previous studies have shown the overexpression of hepsin in prostate cancer, and the dysregulation of hepsin promotes cancer cell proliferation, migration, and metastasis in vitro and in vivo. The review incorporated with our work showed that hepsin expression levels were specifically increased in prostate cancer, and higher expression in metastatic tumors than in primary tumors was also observed. Moreover, increased expression was associated with poor outcomes for patients with prostate cancer. Using in silico protein–protein interaction prediction, mechanistic analysis showed that hepsin interacted with eight other oncogenic proteins, whose expression was significantly correlated with hepsin expression in prostate cancer. The oncogenic functions of hepsin are mainly linked to proteolytic activities that disrupt epithelial integrity and regulatorily interact with other genes to influence cell-proliferation, EMT/metastasis, inflammatory, and tyrosine-kinase-signaling pathways. Moreover, genomic amplifications of hepsin, not deletions or other alterations, were significantly associated with prostate cancer metastasis. Targeting hepsin using a specific inhibitor or antibodies significantly attenuates its oncogenic behaviors. Therefore, hepsin could be a novel biomarker and therapeutic target for prostate cancer.
BackgroundTo explore the underlying mechanism of programmed cell death (PCD)-related genes in patients with endometrial cancer (EC) and establish a prognostic model.MethodsThe RNA sequencing data (RNAseq), single nucleotide variation (SNV) data, and corresponding clinical data were downloaded from TCGA. The prognostic PCD-related genes were screened and subjected to consensus clustering analysis. The two clusters were compared by weighted correlation network analysis (WGCNA), immune infiltration analysis, and other analyses. The least absolute shrinkage and selection operator (LASSO) algorithm was used to construct the PCD-related prognostic model. The biological significance of the PCD-related gene signature was evaluated through various bioinformatics methods.ResultsWe identified 43 PCD-related genes that were significantly related to prognoses of EC patients, and classified them into two clusters via consistent clustering analysis. Patients in cluster B had higher tumor purity, higher T stage, and worse prognoses compared to those in cluster A. The latter generally showed higher immune infiltration. A prognostic model was constructed using 11 genes (GZMA, ASNS, GLS, PRKAA2, VLDLR, PRDX6, PSAT1, CDKN2A, SIRT3, TNFRSF1A, LRPPRC), and exhibited good diagnostic performance. Patients with high-risk scores were older, and had higher stage and grade tumors, along with worse prognoses. The frequency of mutations in PCD-related genes was correlated with the risk score. LRPPRC, an adverse prognostic gene in EC, was strongly correlated with proliferation-related genes and multiple PCD-related genes. LRPPRC expression was higher in patients with higher clinical staging and in the deceased patients. In addition, a positive correlation was observed between LRPPRC and infiltration of multiple immune cell types.ConclusionWe identified a PCD-related gene signature that can predict the prognosis of EC patients and offer potential targets for therapeutic interventions.
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