Abstract

Type 2 transmembrane serine protease (TMPRSS2) is a new member of the serine proteases, and studies have shown that TMPRSS2 plays a role in the occurrence of prostate malignancies and is closely related to the occurrence of the coronavirus disease 2019 (COVID-19). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. To better explore its function in PRAD, we examined the expression level of TMPRSS2 in the GEO, tumor immune assessment resource (TIMER), as well as Oncomine databases and studied the association between TMPRSS2 and overall survival (OS) rates in the UALCAN and gene expression profiling interactive analysis (GEPIA) databases. In addition, we studied the correlation of the level of immune infiltration and markers of immune cell type in the TIMER database, analyzed the prognosis based on the expression level of TMPRSS2 in the related immune cell subsets, and determined the methylation profile of TMPRSS2 promoter by UALCAN database. Subsequently, we conducted a survival analysis and gene ontology (GO) pathway analysis in the TISID database and detected the expression of TMPRSS2 in the Human Protein Atlas (HPA) database. We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. Additionally, we used the microarray GSE56677 and GSE52920 to illustrate changes in TMPRSS2 expression in vivo and in vitro after severe acute respiratory syndrome-coronavirus (SARS-COV) infection, finding that expression of TMPRSS2 decreased after SARS-COV infection in vitro. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. In addition, tumor tissue from COVID-19 patients with PRAD may be more susceptible to infection with SARS-COV-2, which may render the prognosis gets worse.

Highlights

  • Prostatic adenocarcinoma (PRAD) is one of the most common causes of cancer-related death in men in the United States (Gupta et al, 2000)

  • Based on the The Cancer Genome Atlas (TCGA) database, the gene was enriched in prostate cancer in the Human Protein Atlas (HPA) database (Figure 3B), and RNA tissue specificity was enriched in prostate cancer (Figure 3C)

  • This study analyzed the changes of TMPRSS2 mRNA in prostatic adenocarcinoma (PRAD) via the Oncomine, tumor immune assessment resource (TIMER) and GEO databases and explored the correlation between TMPRSS2 and immune infiltration (Figure 12)

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Summary

Introduction

Prostatic adenocarcinoma (PRAD) is one of the most common causes of cancer-related death in men in the United States (Gupta et al, 2000). Prostate cancer is one of the leading causes of morbidity and mortality in men 50 years of age, whose incidence rate varies in different countries and ethnic groups (Parsons et al, 2001). In 2012, the incidence of prostate cancer in the tumor registration areas of China was 9.92/100,000, ranking sixth in male malignant tumors. The prostate consists of two components: the epithelium and the stroma. The interaction between the epithelial cells and the stroma is a key factor in the maintenance of normal function and homeostasis of the prostate (Cunha, 2008). Before developing specific drugs, exploring the occurrence mechanism and identifying new tumor biomarkers with high sensitivity and specificity are crucial in addressing PRAD

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