TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019

Lianxiang Luo; Yushi Zheng; Mingyue Li; Xinjie Lin; Xiaodi Li; Xiaoling Li; Liao Cui; Hui Luo

doi:10.3389/fgene.2020.575770

TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019

Front Genet. 2020 Sep 30:11:575770. doi: 10.3389/fgene.2020.575770. eCollection 2020.

Authors

Lianxiang Luo^{1

2}, Yushi Zheng³, Mingyue Li⁴, Xinjie Lin³, Xiaodi Li³, Xiaoling Li⁵, Liao Cui⁶, Hui Luo¹

Affiliations

¹ The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China.
² The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, China.
³ The First Clinical College, Guangdong Medical University, Zhanjiang, China.
⁴ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
⁵ Animal Experiment Center, Guangdong Medical University, Zhanjiang, China.
⁶ Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, China.

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.

Keywords: coronavirus disease 2019; immune infiltration; prognostic biomarker; prostatic adenocarcinoma; type 2 transmembrane serine protease.