003), and it was positively correlated with macrophages (r = 0.178, p = 2.55e Linear univariate and multivariate regression models were built from TCGA HNSCC patients considering TMPRSS2 as outcome variable. Transmembrane serine protease 2 (TMPRSS2) is a cell surface protein primarily expressed by endothelial cells across the respiratory and digestive tracts. Logrank inspection and Mantel-Cox test were used to generate the survival curve, including OS and relapse-free survival (RFS). Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Transmembrane protease serine 2 (TMPRSS2) is a plasma membrane-anchored serine protease encoded by TMPRSS2 gene in humans. Rev. In this study, we used HPA database to analyze the protein expression and immunohistochemistry (IHC) of TMPRSS2 in normal tissues and PRAD tissues. The TMPRSS2: ERG fusion transcripts in urine samples were found to be one of the most advanced urine-based prostate cancer (PCa) early detection biomarkers. The ERG overexpression induced by TMPRSS2-ERG gene fusion contributes to the development of prostate cancer. p < 0.05, ** One study showed that considering the high incidence of prostate cancer and the high frequency of such gene fusion, the most common genetic abnormality described thus far in human malignancies is tmprss2-ets gene fusion (Rubin and Chinnaiyan, 2006). 160, 439446. Membranous expression in prostate, gastrointestinal tract, kidney and pancreas. The results showed that the expression level of TMPRSS2 had an effect on the prognosis of PRAD. Figure 11. 85, 41224134. TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. (A) GSE12484 healthy vs. peridontitis neutrophils up. The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location. The TIMER database based on the TCGA database was used to reveal that TMPRSS2 was also significantly elevated in PRAD (Figure 1D), suggesting that tumor tissues in PRAD were more susceptible to SARS-COV-2 infection. 4 there is strong expression (I) GSE6674 anti igm vs. cpg stim B cell dn. [9], The fact that severe illness and death from Sars-Cov-2 is more common in males than females, and that TMPRSS2 is expressed several times more highly in prostate epithelium than any tissue, suggests a role for TMPRSS2 in the gender difference. We calculated the Cox P/log-rank p value and hazard ratio with 95% intervals. TMPRSS2-210. doi: 10.1093/bioinformatics/btz210, Rubin, M. A., and Chinnaiyan, A. M. J. L. I. 7:e1002315. Federal government websites often end in .gov or .mil. (G) GSE8515 il1 vs. il6 4 h stim mac up. SARS-COV reduced the expression levels of TMPRSS in (A) GSE52920 and (B) GSE56677 lungs. Cao X, Tang Z, Huang F, Jin Q, Zhou X, Shi J. Oncotarget. In this study, the expression level of TMPRSS2 in PRAD was analyzed using the oncology database. The prostate consists of two components: the epithelium and the stroma. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. The methylation level of TMPRSS2 promoter in normal tissue was significantly higher than that in PRAD. Furthermore, wild-type mice have a strong expression of antigen-positive cells in the bronchiolar epithelial, but this expression was very weak in TMPRSS2-/- mice. Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. A., Alvarez, E., Oliveros, J. C., et al. doi: 10.1002/(sici)1097-0045(20000101)42:1<73::aid-pros9>3.0.co;2-g, Heyn, H., and Esteller, M. (2012). GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers. This fusion separates the ERG 3-prime centromeric regions from the 5-prime telomeric ends; deletions of this region can also occur. doi: 10.1158/0008-5472.CAN-05-2702, Rhodes, D. R., Kalyana-Sundaram, S., Mahavisno, V., Varambally, R., Yu, J., Briggs, B. At the same time, researchers later found that the gene was expressed primarily in the prostate in an androgen-dependent manner. The TMPRS22 and ERG genes are arranged tandemly on chromosome 21q22. We use cookies to enhance the usability of our website. (accessed December 11, 2022). "What is TMPRSS2?". (2005). In this study, clinical data from TCGA3RNA-seq in UALCAN4 and clinical data from 31 cancer types were used to analyze the characteristics of tumor and normal samples in a single other clinic pathological stage, as well as the relative expression of different genes in the tumor subgroup (Chandrashekar et al., 2017). 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. As the consequence in Figure 5, it suggested that high levels of TMPRSS2 mRNA expression were associated with high immune infiltration in PRAD. (A) Eosinophil_abundance, (B) Macrophase_abundance, (C) NKT_abundance, (D) MDSC_abundance, (E) Mem_B_abundance, (F) Act_B_abundance, (G) Treg_abundance, (H) Th2_abundance, (I) Tem_CD8_abundance, (J) Tcm_CD4_abundance, (K) Tfh_abundance, and (L) Th1_abundance. The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. A computational method known as gene set enrichment analysis (GSEA) was used to analyze the signature gene function and potential pathway. Serine proteases are known to be involved in many physiological and pathological processes. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. This coronavirus has been recognized by the World Health Organization as a public health emergency of international concern. Vero E6-TMPRSS2-T2A-ACE2 cells in 96-well plates in duplicate and incubated for 1 h at 37 C. He is based in the Department of Infection, Immunity & Cardiovascular Disease in the Faculty of Medicine at Sheffield. (2007). The robotic device and associated on-screen software suite aim to make hand movement recovery quicker and easier for patients. In the past decade, several genes associated with prostate cancer have been identified. One symptom associated with COVID-19 is diarrhea and abdominal pain in many patients, often preceding respiratory symptoms. Currently, . It was found not to be effective against COVID-19. Official gene symbol, which is typically a short form of the gene name, according to HGNC. Among its related pathways are Early SARS-CoV-2 Infection Events and SARS-CoV-2 Infection . 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). Careers. No use, distribution or reproduction is permitted which does not comply with these terms. doi: 10.1038/nrg3270, Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krger, N., Herrler, T., Erichsen, S., et al. Useful information about the protein provided by UniProt. 11 December 2022. (2011). doi: 10.1006/geno.1997.4845, Parsons, J. K., Gage, W. R., Nelson, W. G., and De Marzo, A. M. (2001). MeSH Immunohistochemistry (IHC) of TMPRSS2 expression in prostatic adenocarcinoma (PRAD) tissues and corresponding normal tissues based on the Human Protein Atlas (HPA). Prostate specific membrane antigen (PSMA) is overexpressed in prostatic adenocarcinoma (CaP), and its expression is negatively regulated by androgen stimulation. Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3. Bioinformatics approach leads to the discovery of the TMPRSS2: ETS gene fusion in prostate cancer. Certain viruses, especially coronaviruses including SARS-CoV (that causes SARS), MERS-CoV (causes MERS), and SARS-CoV-2 (which causes COVID19), require TMPRSS2 for their entry into the body. TMPRSS2-ERG fusion gene is the most frequent, present in 40% - 80% of prostate cancers in humans. The present study aimed to investigate the significance of the TMPRSS2:ERG gene fusion in human prostate cancers using bioinformatics tools. Correlation between TMPRSS2 and patient survival. Products Background Distributor Information 2. The mechanisms of olfactory dysfunction in COVID-19 are still unclear. The presence of TMPRSS2-ERG compared to a wild-type background was associated with a stemness phenotype and with relatively increased RAS-induced differential gene expression for MYC and. [18][19] Prostate cancer patients receiving androgen deprivation therapy have a lower risk of SARS-CoV-2 infection than those not receiving that therapy. In general, TMPRSS2 primarily affects tumor metastasis by intervening in the signaling pathway, but the mechanism of its influence on the prognosis of PRAD is still unclear. and c-Myc, as well as inhibiting key downstream genes, including PSA and TMPRSS2. Further studies on immune cell type marker PRAD (Table 1) showed that the expression level of TMPRSS2 mRNA was correlated with B-cells (CD19, CD27, and CD38), and CD8+ in PRAD T-cells (CD8A and CD8B), neutrophil granulocytes (FCGR3B, SIGLEC5, and S100A12), macrophages (CD84 and CD163), Th1 (STAT4 and STAT1), Treg (STAT5B and TGFB1), and T-cell failure (PDCD1, CTLA4, LAG3, and GZMB) were significantly correlated, suggesting that these results strongly confirm the close correlation between TMPRSS2 and immune infiltration of PRAD. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). We obtained the SARS-COV-related microarray, GSE30589 (Dediego et al., 2011), GSE56677 (Selinger et al., 2014), and GSE52920 (Jimenez-Guardeno et al., 2014) expression profiles and the prostatic-related microarray GSE6956 (Wallace et al., 2008) in the GEO database,8 a microarray form of high-throughput functional genomics data for public knowledge base storage. Please note that medical information found Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. However, we found that TMPRSS2 might influence the prognosis of PRAD through a new mechanism, namely, immune infiltration, which suggests a direction for further studies. Table 1 TMPRSS2 gene association with immune signature, MYC and MYC signature, HPV status and P53 mutation in HNSCC patients. Why not the coronavirus too?Throughkatherine j wuJuly 25, 2022As the Omicron variant spread across the United States this past Christmas, Mary Carrington unknowingly found herself at a superspread event: a cl. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. TMPRSS2-204. Cancer Res. Changes in TMPRSS2 expression levels caused by single nucleotide polymorphisms (SNPs) may contribute to the outcome of COVID-19. The protein expression of TMPRSS2 was significantly reduced in normal tissue, and the protein level was significantly elevated in tumor tissue (Figures 2AD). Cancer Res. 2020). (2013). GeneCards - The Human Gene Compendium Figure 8. Osman is a Postdoctoral Research Associate at the University of Sheffield studying the impact of cardiovascular disease (atherosclerosis) on neurovascular function in vascular dementia and Alzheimer's disease using pre-clinical models and neuroimaging techniques. GTEx database9 is a database that supplies tissue RNA-Seq data and SNP information contributed by healthy people and combines SNP information and gene expression level. More specifically, TMPRSS2 can cleave the SARS-COV-2 spike protein, facilitating viral entry and activation (Strope et al., 2020), and TMPRSS2-expressing cell lines are highly susceptible to SARS-COV, Middle East respiratory syndrome-coronavirus (MERS-COV), and SARS-COV-2 (Matsuyama et al., 2020), which prompted us to explore the association between TMPRSS2 and SARS-COV-2, especially in PRAD patients. (ACE2 and TMPRSS2). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Membrane-Anchored Serine Proteases in Health and Disease. ACE2 as the entry receptor and TMPRSS2 as the S protein primer can promote the process of SARS-S . CCS1477, a clinical candidate, causes complete tumour growth inhibition in a 22Rv1 xenograft model at doses which are well tolerated. Figure 4. GSE52920 contains three biological sample types (SARS-COV-wt, SARS-COV-mutPBM, and Mock) based on mice lung tissue. What are the Applications of Technology-Based Mental Health Interventions? TMPRSS2-202. (B) RNA expression of TMPRSS2 in different cancers in the HAC database. NewsMedical spoke to Waduda Parolari Musaid at MEDICA 2022 about Gloreha's robotics-assisted neurorehabilitation solutions. DNA methylation profiling in the clinic: applications and challenges. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. The expression of SARS-CoV-2 spike (S) glycoprotein protein was readily detected in patchy areas of human liver and biliary organoids, but not in uninfected control by immunofluorescence staining ( figure 1C; online supplemental figure 1C ). Diseases associated with TMPRSS2 include Covid-19 and Influenza . CD8+ T-cell, neutrophil, and dendritic cell were connected with high expression and good prognostic value. J. Virol. Top expressed in: body of pancreas; rectum; prostate; parotid gland; duodenum; pylorus; upper lobe of left lung The TMPRSS2/ERG fusion joins TMPRSS2 exons 1 or 2 usually to ERG exons 2, 3 or 4, which results in activation of the ERG transcription factor. Genomics 44, 309320. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Overall, these results suggested that TMPRSS2 and its associated genes were important for immune cell infiltration in the PRAD microenvironment and possibly have a more significant effect on the prognosis of PRAD. doi: 10.4161/rna.8.2.15013, Glowacka, I., Bertram, S., Muller, M. A., Allen, P., Soilleux, E., Pfefferle, S., et al. TMPRSS2 (PRSS10) protein expression summary. sharing sensitive information, make sure youre on a federal Tomlins, S. A. et al. However, in VCaP ERG shRNA (low ERG) cells, enzalutamide did not inhibit the TMPRSS2 gene expression at 5 M concentration and all other genes were inhibited to a lower extent compared to ERG intact . The image and the chart are clickable and will redirect to more Tissue data. The encoded protein contains a type II transmemb, Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to. Isoindolinone motifs have been a central part of many pharmacological compounds, and their derivatives possess substantial anticancer . J. Virol. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues. Tumor immunobiological differences in prostate cancer between African-American and European-American men. Prostate 42, 7378. 04; Figure 5A). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. *Correspondence: Lianxiang Luo, luolianxiang321@163.com, luolianxiang321@gdmu.edu.cn, Coronavirus Disease (COVID-19): Molecular Mechanisms, Translational Approaches and Therapeutics, View all (2014). (A) mRNA expression of TMPRSS2 in GEO. . TMPRSS2 Species H. sapiens (human) Insert Size (bp) 1479 Entrez Gene TMPRSS2 ( a.k.a. Moreover, it is worth noting that all analyses in this paper are based on servers or databases, which may vary in the specific experimental process. 2017 Dec 15;186(12):1352-1361. doi: 10.1093/aje/kwx235. Besides, as shown in the Figures 9BE, the results is as same as the Figure 9A that the methylation level of TMPRSS2 promoter in normal group was significantly higher than other the groups of race, age, lymphatic metastatic status and TP53 mutation status. TMPRSS2-ERG fusions have been shown to regulate AR signaling, interfere with pro-differentiation functions, and mediate oncogenic signaling. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. Afar, D. E. H., Vivanco, I., Hubert, R. S., Kuo, J., Chen, E. I., Saffran, D. C., et al. 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). In addition, TMPRSS2 is a candidate proteolytic activated human influenza virus, which might play an important role in screening other progenitors in the future (Bttcher et al., 2006). High TMPRSS11D protein expression predicts poor overall survival in non-small cell lung cancer. Table 2. doi: 10.1371/journal.ppat.1002315, Denison, M. R., Graham, R. L., Donaldson, E. F., Eckerle, L. D., and Baric, R. S. J. R. B. Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene. The TISIDB database, known as a portal for interaction between the tumor and immune systems, integrates 988 reported immune-related anti-tumor genes, high-throughput screening techniques, molecular profiling and paracancer multinomics data, and various immunological data resources retrieved from seven public databases (Ru et al., 2019). 8600 Rockville Pike Figure 12. doi: 10.1158/0008-5472.CAN-07-2608, Wardefarley, D., Donaldson, S. L., Comes, O., Zuberi, K., Badrawi, R., Chao, P., et al. To probe the cause of the increased TMPRSS2 in PRAD, we studied the methylation levels of TMPRSS2 in PRAD and found that the promoter methylation levels of TMPRSS2 in LUAD decreased significantly. GEPIA is an interactive network consisting of 9,736 tumor samples and 8,587 normal samples from the TCGA and GTEx projects that analyzed RNA sequencing expression (Tang et al., 2017). TMPRSS2 is an endothelial cell surface protein that is involved in the viral entry and spread of coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the virus that causes COVID19. As of August 28, 2020, more than 24.2 million confirmed cases have been reported across more than 200 countries and territories, resulting over 820,000 deaths (according to data from Johns Hopkins University) and causing a notable negative impact on human health and economic development. GSE56677 contained gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-COV strains obtained from human patients, MERS-COV-EMC (designated EMC) and MERS-COV-London (designated LoCoV). Using this database, we constructed the gene interaction network of TMPRSS2 for coexpression, colocalization and genetic interaction and systematically evaluated its function. (2020). Serine proteases are known to be involved in many physiological and pathological processes. Evidence has shown that SARS-CoV-2 can infect intestinal enteroids. TMPRSS2 is a membrane associated serine protease, expressed in the epithelium of the human respiratory tract and prostate glands. doi: 10.1038/labinvest.3700477, Sanders, J. M., Monogue, M. L., Jodlowski, T. Z., and Cutrell, J. The transmembrane protease serine 2:vets erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion is common in prostate cancer, while its functional role is not fully understood. rane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. More evidence is needed to substantiate whether SARS-CoV-2 can be transmitted from feces. Cell membranes anchor DPP4 along with Transmembrane Protease Serine Protease-2 (TMPRSS2) via CD-9 . Correlation analysis between PRAD and related gene markers of immune cells. 2021. The results showed that prostate adenocarcinoma patients with a high level of TMPRSS2 expression, and Gleason score exhibited a longer survival period (Figure 4E). Both ACE2 and TMPRSS2 are expressed in nasal, bronchial, and gastrointestinal epithelium. p < 0.01, and *** TISIDB: an integrated repository portal for tumorimmune system interactions. 2019 Jun 8;20(11):2802. doi: 10.3390/ijms20112802. The higher expression level suggests that TMPRSS2 possesses diverse functions in various tumors, especially in PRAD. Nat. (2020). Serine proteases are known to be involved in many physiological and pathological processes. We identified that Go-Ichi-Ni-San complex subunit 1 (GINS1) is the potential therapeutic target in Cancer/COVID-19 by GEPIA. 45, 580585. All authors contributed to the article and approved the submitted version. GO and KEGG analyses and visualization were implemented based on R software (Version 3.6.1). ERG overexpression contributes to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling. Cancer and COVID-19: unmasking their ties. The classification rules are the same used for the tissue specificity category. Publication types Review MeSH terms Gene Fusion* Humans Male Prostatic Neoplasms / enzymology In our future research, it will be important to verify the analysis results through experiments. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. ** This product is for in vitro and research use only. Triplicate wells of Calu-3 2B4 cells were infected with Human Coronavirus EMC 2012 (HCoV-EMC) or time-matched mock infected. Natl. TMPRSS2 Gene Functional Associations TMPRSS2 has 3,397 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 66 datasets. doi: 10.1007/s10549-016-4013-7, Li, T., Fan, J., Wang, B., Traugh, N., Chen, Q., Li, J. S., et al. 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. Table 3. Purpose TMPRSS2-ERG gene fusions are frequently found in prostate cancer and are pathognomonic for prostatic origin. Genet. -L., Wang, X. Neoplasia 9, 166180. In addition, GSE56677 and GSE52920 were used to study the expression changes of TMPRSS2 in vivo and in vitro after SARS-COV infection. One-stop service from gene synthesis and vector construction to protein expression and purification. doi: 10.1126/science.aan2507, Vaarala, M. H., Porvari, K., Kellokumpu, S., Kyllonen, A. P., and Vihko, P. J. T. J. O. P. (2001). Int J Mol Sci. Serine proteases are known to be involved in many physiological and pathological processes. 38, W214W220. government site. The effect of thiol drugs on Vero E6-TMPRSS2 cells during the 2 h of SARS-CoV-2 infection was evaluated by the addition of 6.25 mM of each drug and 63.2 TCID 50 /mL SARS-CoV-2 simultaneously to Vero E6-TMPRSS2 cell monolayer in 96-well plates. A new study, published in PLoS Genetics on Dec. 7, 2022, reveals how a selfish gene in yeast uses a poison-antidote strategy that enables its function and likely has facilitated its long-term . Angiotensin-converting enzyme 2 (ACE2) has identified as cell entry receptors for SARS-COV-2, and receptor-mediated virus entry was dependent on TMPRSS2 (Hoffmann et al., 2020; Zhou et al., 2020). Overexpression of mitochondrial serine hydroxyl-methyltransferase 2 is associated with poor prognosis and promotes cell proliferation and invasion in gliomas. PLoS Pathog. (A) RNA methyltransferase activity, (B) TRNA methyltransferase activity, and (C) general transcription initiation factor activity. The higher TMPRSS2 expression level suggests that it possesses diverse functions in various tumors, and we explored its GO function in a GO model of TISIDB database, where we found TMPRSS involved in multiple functions related to virus entry into the host cell and viral life cycle. We use cookies to enhance your experience. 86, 10991102. We set Cox P/log-rank p = 0.05 as the thresholds. Consistent with extensive gene/protein characterization data. The Wilcoxon test and t-test were used to compare the expressions of tumor and normal groups of data. [18][19], Camostat is an inhibitor of the serine protease activity of TMPRSS2. Because it is located on the surface of prostate cells, we found that TMPRSS2 could be a potential marker for prostate cancer diagnosis. Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Cells were harvested at 0, 3, 7, 12, 18, and 24 h post-infection (hpi), RNA extracted, and transcriptomics analyzed by microarray (Selinger et al., 2014). This gene is up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. . Figure 10. To explore whether TMPRSS2 exerts potential biological roles in immune infiltration, we conducted an integrated analysis based on the TIMER and TISIDB databases, analyzing the link between TMPRSS2 and immune cell infiltration as well as gene markers of immune cell subtypes in PRAD. between patient and physician/doctor and the medical advice they may provide. (2020). tmprss2-erg gene fusion was evaluated by fluorescence in situ hybridization (fish) using break-apart probes of the erg gene, as previously described. Since smoking tobacco affects and damages the lungs, it increases the risk of respiratory infections and makes it easier for the coronavirus disease (COVID-19) to invade the lung tissue, causing more severe symptoms and increasing the risk of death. This gene encodes a protein that belongs to the serine protease family. Acad. We also explored the expression of TMPRSS2 between tumor and normal tissues and conducted IHC in the HPA database. Figure 3. TMPRSS2 is widely expressed in the prostate, intestine, stomach, liver, lung, and kidney and so on. The results showed that the expressions of TMPRSS2 in the control group was slightly decreased compared with the other group (Figure 11B), and mice lungs after SARS-COV infection obviously increased compared with the control group (Figure 11A). Cancer 27, R281R292. The biological function of this gene is unknown. Figure 5. A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue section. Currently, no specific antiviral drugs or clinically effective vaccines are available to prevent and treat the coronavirus disease 2019 (COVID-19; Sanders et al., 2020). doi: 10.1038/s41586-020-2012-7, Keywords: type 2 transmembrane serine protease, coronavirus disease 2019, prostatic adenocarcinoma, immune infiltration, prognostic biomarker, Citation: Luo L, Zheng Y, Li M, Lin X, Li X, Li X, Cui L and Luo H (2020) TMPRSS2 Correlated With Immune Infiltration Serves as a Prognostic Biomarker in Prostatic Adenocarcinoma: Implication for the COVID-2019. All authors reviewed the manuscript. Expression of TMPRSS2 was associated with tumor-infiltrating lymphocytes (TILs). Multiple purification systems (30+) to choose. 30 . 14 . The p values of all of the abovementioned cells are less than 0.001, and |rho| The main function of the prostate is to contribute tumour microenvironment (termed . . The TMPRSS2-ERG Fusion FISH Probeis used to confirm a fusion of the TMPRSS2 and ERG genes. Intracellular, Membrane, Secreted (different isoforms), Cell type enhanced (Prostatic glandular cells, Distal enterocytes, Gastric mucus-secreting cells, Proximal enterocytes, Paneth cells), Prognostic marker in renal cancer (favorable) and endometrial cancer (favorable), Prostate cancer - Lipid metabolism (mainly), Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiolog, This gene encodes a protein that belongs to the serine protease family. Additionally, the correlation between TMPRSS2 and immune infiltration in PRAD was analyzed in the TIMER database and TISIDB database. This section contains information regarding the expression profiles of . This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions. [8], Mutations of the TMPRSS2 gene are often involved in prostate cancer. official website and that any information you provide is encrypted The high expression level of TMPRSS2 in the tumor and corresponding normal tissues in cancers was verified via the Oncomine database. The consequence shows that TMPRSS2 expression levels in both of GSE56677 and GSE52920 were reduced after SARS-COV infection (Figure 11), suggesting that TMPRSS2 promoter methylation might be activated and display an increased level in PRAD. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected. All genes with at least one predicted secreted isoform have been annotated and classified with the aim to determine if the corresponding protein(s) are: The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. Retrieved on December 11, 2022 from https://www.news-medical.net/health/What-is-TMPRSS2.aspx. TMPRSS2 participated in the GO function analysis results of GSE30589 and GSE56677. Materials and methods Cell culture and treatment As a serine protease, it is involved in the cleaving peptide bonds of proteins that have serine as the nucleophilic amino acid within the active site. (2005). 10. http://software.broadinstitute.org/gsea/index.jsp, Addeo, A., and Friedlaender, A. BMC Genomics 15:1161. doi: 10.1186/1471-2164-15-1161, Smyth, G. K., Michaud, J., and Scott, H. S. J. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. TMPRSS2-203. (D) GSE35543 in vivo ntreg vs. in vitro itreg up. Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected. News-Medical. (2001). 65, 1166711675. (A) Immunoreactivity of TMPRSS2 in various cancers. A pathology atlas of the human cancer transcriptome. Science 357:eaan2507. Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas. Keywords assigned by UniProt to proteins due to their particular molecular function. However, the prognosis and immune mechanisms of TMPRSS2 in PRAD are still unclear. Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues. Endocr. All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Sungnak and colleagues assessed the transcript expression of genes involved in the viral entry in healthy human donors using single-cell RNA sequencing, and they showed that ACE2 and We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. In this study, we conducted a search based on the following criteria: (A) analysis type: cancer and normal tissue; (B) data type: mRNA; and (C) threshold: fold change = 1.5 and value of p = 0.01. According to whether the mice infected with SARS-COV, we divided it into two groups, SARS-COV group and Mock group and conducted the analysis on the changes of TMPRSS2 expression between two groups. 10(6):779-782. News-Medical.Net provides this medical information service in accordance Methylation is an important event in epigenetic modification of the genome and is closely related to the course of disease. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity. (2006). Increased disease burden and a smaller number of approved targeted therapies are a growing concern worldwide. TMPRSS2 is an androgen responsive transmembrane serine protease. doi: 10.1093/nar/gkx247, Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., and Sun, X. W. (2005). [7] Gene knockout mice lacking TMPRSS2 show no abnormalities. Analysis of TMPRSS2 single-gene gene set enrichment analysis (GSEA) based on C7: immunologic gene sets in GSE30589 and GSE5667. We used GSE56677 and GSE52920 to study the in vivo and in vitro changes of TMPRSS2 after SARS-COV infection. FOIA General information on TMPRSS2 protein . All genes with at least one isoform expected to be secreted to the extracellular environment have been annotated and classified either as secreted to blood or as locally secreted, depending on the predicted final location of the corresponding protein. [11][12] SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. doi: 10.1126/science.1117679, Uhln, M., Fagerberg, L., Hallstrm, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., et al. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). Using the TIMER database,2 this study analyzed the expression of TMPRSS2 in PRAD patients and six types of infiltration of immune cells (B-cells, CD4+ T-cells, CD8+ T-cells, neutrophils, macrophages, and dendritic cells) using an abundance of correlation (Li et al., 2017). 13 the probes, consisting of a rhodamine-labeled 5- erg probe ( bac rp11-95i21) and a fluorescein isothiocyanate-labeled 3- erg probe ( bac rp11-476d17 ), were obtained from children's hospital of Progress in Molecular Biology and Translational Science 99:1-50, Stopsack et al, 2020. Cancer Res. TMPRSS2. At the same time, single-gene GSEA analysis was used to verify our conclusions. (2020). doi: 10.1016/j.cell.2020.02.052, Jimenez-Guardeno, J. M., Nieto-Torres, J. L., Dediego, M. L., Regla-Nava, J. Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity. J. Pathol. The gene TMPRSS2 is closely relevant to prostate cancer as well, regulating many biological processes (Tomlins et al., 2005). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. HHS Vulnerability Disclosure, Help Restrict the view to a region of the gene by dragging across the histogram to highlight the region of interest, or by using the sliders in the filters panel to the left. In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. or actually being attached to membrane or retained in intracellular locations like mitochondria, endoplasmatic reticulum (ER), Golgi apparatus or lysosomes. Lancet 395, 565574. PLoS Pathog. TMPRSS2-ERG fusion is the most common known gene rearrangement in prostate carcinoma. Targets. Proc. J. Clin. doi: 10.1530/ERC-20-0165, Bttcher, E., Matrosovich, T., Beyerle, M., Klenk, H. -D., Garten, W., and Matrosovich, M. (2006). doi: 10.1002/jcph.1641, Tang, Z., Li, C., Kang, B., Gao, G., Li, C., and Zhang, Z. J. N. A. R. (2017). Several reports (mainly case series) from around the world have concluded that patients with malignant tumors seem to be more vulnerable to severe COVID-19 infection and death (Addeo and Friedlaender, 2020; Van De Haar et al., 2020), especially those with precancerous conditions (Bhowmick et al., 2020). The exact biological function of TMPRSS2 is largely unknown, although research has shown that it is involved in certain pathologies (outlined below). The results (Figure 1A) showed that the expression of TMPRSS2 in prostate cancer tissues was significantly higher than that in normal tissues (value of p < 0.001) GES6956 further proves the higher result in prostate cancer compared with normal tissue. Cancer Res. GENEMANIA5 is a network interface for hypothesis deduction based on gene function (Wardefarley et al., 2010). An equal volume of 1.5% Methyl Cellulose 400 (FUJIFILM Wako Pure Chemical Corporation) in culture . doi: 10.1593/neo.07112, Ru, B., Wong, C. N., Tong, Y., Zhong, J. Y., Zhong, S. S. W., Wu, W. C., et al. The androgen-regulated TMPRSS2 promoters form a fusion gene with coding regions of the proto-oncogenic ETS transcription factor family members, which are closely related to prostate cancer and regulate many biological processes (Tomlins et al., 2005). Specifically, TMPRSS2 fuses with ERG; an oncogenic (cancer-promoting) transcription factor. Nat. and transmitted securely. In addition, convalescent sera from SARS patients (sera from recovered patients) that contains specific neutralizing antibodies against SARS-CoV S-protein; the spike domain, can neutralize SARS-CoV-2 albeit with lower efficiency compared to SARS-CoV. Blocking TMPRSS2 could potentially be an effective clinical therapy for COVID-19. It is used to treat pancreatitis and reflux esophagitis. Use of within-array replicate spots for assessing differential expression in microarray experiments. When combined with urinary marker PCa antigen 3 (PCA3), urinary TMPRSS2: ERG has been reported to provide high specificity and sensitivity in diagnosing PCa [ 23 ]. Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer in the world and the most prevalent cancer of developing countries. 60, 801807. In late December 2019, a case of viral pneumonia caused by a novel coronavirus was reported in Wuhan, Hubei province, China (Lu et al., 2020). Samples from prostate cancer patients show an upregulation of TMPRSS2 in response to androgens. [17] The fact that TMPRSS2 has no known irreplaceable function makes it a promising target for preventing SARS-CoV-2 virus transmission. TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences. (2020). 193, 134140. [15], A TMPRSS2 inhibitor such as camostat approved for clinical use blocked entry and might constitute a treatment option. (2017). The TMPRSS2-ERG gene fusion in primary prostate cancer. TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. 45, W98W102. After correcting the tumor purity, the immune cell type markers in PRAD were further studied. Due to the high homology between SARS-COV-2 and SARS-COV, changes in TMPRSS2 expression in cells or animals infected with SARS-COV can be used as a reference for SARS-COV-2 infection (Zhou et al., 2020). We also used the GERIA and UALCAN databases to process survival analysis and found that the expression of TMPRSS2 was not directly associated with PRAD prognosis. However, the prognosis of COVID-19 patients with PRAD is unclear. https://www.news-medical.net/health/What-is-TMPRSS2.aspx. Cell. When the gene, called WWP2, is blocked, heart function is improved and scar tissue formation is slowed, delaying the progression to heart failure. Sci. The RNA data was used to cluster genes according to their expression across cell lines. Therefore, we used the UALCAN database to verify the methylation levels of TMPRSS2 promoter in PRAD. (2010). Received: 24 June 2020; Accepted: 07 September 2020; Published: 30 September 2020. 47 In this study, we performed an extensive BLASTP search to identify ACE2 and TMPRSS2 gene homologs in lower vertebrate classes (cyclostomata, fishes, amphibians, reptiles, birds,) and each order and family in mammals. Are medical masks non-inferior to N95 respirators to prevent COVID-19 in health care workers providing routine care? Disease related keywords assigned by UniProt combined with Cancer-related genes and FDA approved drug targets, Useful information about the gene from Entrez. Cancer Treat. This site complies with the HONcode standard for trustworthy health information: verify here. doi: 10.1016/j.neo.2017.05.002, Cunha, G. R. (2008). Explore the latest full-text research PDFs, articles, conference papers, preprints and more on GENE KNOCKOUT. In the current study, the frequency of TMPRSS2 rs12329760 CC than TT genotypes was significantly lower in improved patients than in dead patients. Cell 181, 271.e8280.e8. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Bhowmick, N. A., Oft, J., Dorff, T., Pal, S., Agarwal, N., Figlin, R. A., et al. It has been shown to activate hemagglutinin proteins of human influenza viruses and is implicated in prostate carcinogenesis. Figure 2. 13) and CD8+ T-cells (r = 0.16, p = 1.07e [14], The enzyme Adam17 has similar ACE2 cleavage activity as TMPRSS2, but by forming soluble ACE2, Adam17 may actually have the protective effect of blocking circulating SARSCoV2 virus particles. 118 Articles, This article is part of the Research Topic, https://doi.org/10.3389/fgene.2020.575770, http://software.broadinstitute.org/gsea/index.jsp, Creative Commons Attribution License (CC BY). . doi: 10.1016/s0090-4295(01)01311-5, Pchejetski, D., Golzio, M., Bonhoure, E., Calvet, C., Doumerc, N., Garcia, V., et al. LL and YZ wrote the manuscript. In this interview, we speak with University of Warwick spin-out Cryologyx about their innovative new technology that hopes to revolutionize cell-based assays for researchers across life sciences and drug discovery. Complete information for lnc-TMPRSS2-6 gene (RNA Gene), , including: function, proteins, disorders, pathways, orthologs, and expression. Abstract. [14] Hydroxychloroquine inhibits the action of cathepsin L in endolysosomes, but because cathepsin L cleavage is minor compared to TMPRSS2 cleavage, hydroxychloroquine does little to inhibit SARS-CoV-2 infection. RNA Biol. The remaining cancer tissues were all negative. 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. HealthScientists have known for decades that some people can be resistant to HIV infection. According to the above analysis, we observed a significant increase of TMPRSS2 expression in PRAD, and as a consequence, a further study was performed to explore the reason for the elevated TMPRSS2. (A,B) Normal prostate (T-77100) tissue; (C,D) prostate (T-77100) tumor tissue. As mentioned, TMPRSS2 is also expressed across the gastrointestinal (digestive) tract, such as in intestinal epithelial cells which are the targets for many enteric (gut) viruses. TMPRSS2-ERG is the most frequent oncogenic gene fusion rearrangement in prostate cancer: It has been observed in almost half of prostate cancer patients and detected in about one-quarter of patients with prostatic intraepithelial neoplasia. TMPRSS2 protein's function in prostate carcinogenesis relies on overexpression of ETS transcription factors, such as ERG and ETV1, through gene fusion. JAMA 323, 18241836. This review focuses on the characteristics, oncogenic and rearranged mechanism, and clinical application of TMPRSS2-ETS gene fusions. Zang et al, 2020. As shown in Figure 3A, prostate cancer, selected renal cell cancers, urothelial carcinoma, lung cancer, colorectal cancer, and pancreatic cancer exhibit weak to moderate membranous or granular cytoplasmic immunoreactivity. 0.2. A novel inhibitor of TMPRSS2 has been found to be effective against SARS-CoV-2 infection in cell and animal models. Med. At the same time, the correlation between TMPRSS2 expression and the genetic markers of tumor infiltrating immune cells was also discussed. Protein-protein interaction (PPI) network in GENEMANIA database. Copyright 2020 Luo, Zheng, Li, Lin, Li, Li, Cui and Luo. p < 0.01, and *** Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium. 80, 98969898. General description of the gene and the encoded protein (s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project. LL conceived the idea. Owned and operated by AZoNetwork, 2000-2022. Number of protein-coding transcripts from the gene as defined by Ensembl. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). Would you like email updates of new search results? Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. Results The transmembrane serine protease 2 (TMPRSS2) is the major host protease that enables entry of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) into host cells by spike (S) protein priming. -G., Hu, B., Zhang, L., Zhang, W., et al. Am J Epidemiol. 181(2): 271280.e8. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis Prostate cancer is very common in elderly men in developed countries. The aim was to investigate the association between TMPRSS2 gene polymorphisms and the . doi: 10.1073/pnas.2002589117, Nam, R. K., Sugar, L., Yang, W., Srivastava, S., Klotz, L. H., Yang, L. Y., et al. We used the GEPIA database to examine the prognostic value of TMPRSS2. Figure 1. Three separate tumor foci, two in the peripheral zone and one in the transition zone, are present in a cross-section of the prostate (A). Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen YT. What is TMPRSS2?. [10], Some coronaviruses, e.g. (2014). This study analyzed the changes of TMPRSS2 mRNA in PRAD via the Oncomine, TIMER and GEO databases and explored the correlation between TMPRSS2 and immune infiltration (Figure 12). The site is secure. in terms of normal function, tmprss2 has been associated with physiological and pathological processes such as digestion, tissue remodelling, blood coagulation, fertility, inflammatory responses, tumour cell invasion, apoptosis and pain. p < 0.05, ** The effect of ubiquitination on SARS-CoV-2 infection and patient prognosis, https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMPRSS2, https://www.sciencedirect.com/science/article/pii/B9780123855046000014, https://pubmed.ncbi.nlm.nih.gov/32276929/, https://pubmed.ncbi.nlm.nih.gov/32142651/, https://pubmed.ncbi.nlm.nih.gov/32404436/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401451/, COVID-19 pandemic caused rapid brain aging in adolescents, COVID-19 vaccines may reduce long-COVID symptoms, Characterization of SARS-CoV-2 Omicron BQ.1.1, SARS-CoV-2 Omicron infections pose long-COVID risks despite reduced severity, COVID-19 vaccination may cause temporary menstrual disturbances in adolescent girls, The prevalence and risk factors of pediatric post-COVID in a population-based sample, Researchers uncover the host protease CAPN2 as a novel host factor that aids the infection of SARS-CoV-2, Exploring effects of COVID-19 pandemic on neurodevelopment and mental health in adolescents. PRAD: (A) sample type, (B) race, (C) age, (D) lymphatic metastatic status, and (E) TP53 mutation status (* Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. 93(6):e01815-18. All brain expression profiles are based on data from HPA. . In this study, interaction analysis was conducted on online database GEPIA3 to study the expression of PRAD based genes. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected. J. TMPRSS2 is expressed in prostate epithelial cells and is needed for normal prostate function. TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer. The prognostic value and OS rate of TMPRSS2 in PRAD were analyzed via the gene expression profiling interactive analysis (GEPIA) and UALCAN databases to explore its functional mechanism. COVID-19 and androgen targeted therapy for prostate cancer patients. Gene namei. TMPRSS2 is essential for the cell entry of influenza viruses and coronaviruses, including SARS-CoV, SARS-CoV-2 and MERS. The .gov means its official. The tumour growth inhibition caused by CCS1477 is sustained following drug withdrawal. doi: 10.1016/S0140-6736(20)30251-8, Matsuyama, S., Nao, N., Shirato, K., Kawase, M., Saito, S., Takayama, I., et al. TMPRSS2-ERG gene fusion functions as a biomarker for prostate cancer, which can be easily detected in urine. Mucci, L. A. et al. The patients were divided into two groups based on the median level of TMPRSS2 expression in each queue. The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. doi: 10.1093/nar/gkq537, Wu, M., Wanggou, S., Li, X., Liu, Q., and Xie, Y. . Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells ( PubMed: 15537383, PubMed: 26018085, PubMed: 25122198 ). 10, 37813788. Clipboard, Search History, and several other advanced features are temporarily unavailable. This protein also facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. B. (C) GSE41867 day 6 vs. day 15 lcmv clone13 effect or CD8 T-cell up. Four such genes: the ETS-related gene (ERG), The Transmembrane Protease Serine 2 (TMPRSS2), Mouse double minute 2 homolog (MDM2), and Phosphatase and tensin homolog (PTEN) have gained recognition for their high specificity of expression in prostatic carcinomas. Only bands not corresponding to the predicted size. PMC Therefore, before developing specific drugs, exploring the occurrence mechanism and identifying new tumor biomarkers with high sensitivity and specificity are crucial in addressing PRAD. doi: 10.1158/0008-5472.CAN-17-0307, Lonsdale, J. T., Thomas, J., Salvatore, M., Phillips, R., Lo, E., Shad, S., et al. This drug is approved for clinical use already in Japan for unrelated illnesses and could serve to be an important therapy for COVID-19. Rev. Interestingly, TMPRSS2 is also necessary for SARS-CoV-2 cell entry [29,30]. (2011). Fold change = 1.5, value of p = 0.01, and a top 10% of gene rankings; and (D) different TMPRSS2 expressions between tumor and adjacent normal tissues. GENERAL INFORMATIONi. The prostatic-related microarray GSE6956 contains gene expression profiles of primary prostate tumors resected from 69 patients and 18 non-tumor prostate tissues. These contain the genes encoding the spike protein, RNA replicase, 3 C-like protease, . (A) Correlation between TMPRSS2 expression and immune cell infiltration in PRAD. TMPRSS2: potential biomarker for COVID-19 outcomes. Notably, TMPRSS2 does not appear to play an essential role in any organ, as other proteases may provide a degree of redundancy. In certain studies, according to the immunohistochemical analysis of clinical specimens, TMPRSS2 has the highest expression in the apex of the prostate, the secretory epithelium of prostate cancer, and the glandular cavity, indicating that TMPRSS2 is a secreted protease that is highly expressed in prostate cancer and prostate cancer, making it a potential target for the treatment and diagnosis of cancer (Afar et al., 2001). This database was used to investigate the gene expression of TMPRSS2 in the prostate gland (Lonsdale et al., 2013). Proteomics. Univariate analysis was performed through GEPIA to assess the impact of TMPRSS2 on various cancer survival rates (Figure 4A). Find methods information, sources, references or conduct a literature review on GENE . TMPRSS2-205. [12][14] Another experimental candidate as a TMPRSS2 inhibitor for potential use against both influenza and coronavirus infections in general, including those prior to the advent of COVID-19, is the overt-the-counter (in most countries) mucolytic cough medicine bromhexine,[16] which is also being investigated as a possible treatment for COVID-19 itself as well. In the normal prostate, TMPRSS2 contributes to proteolytic cascades that result in the activation of prostate-specific antigen, itself a protease involved in ejaculate production ( 9 ). TMPRSS2, which is involved in proteolytic cleavage of ACE2 and the SARS-CoV-2 spike protein, leading to viral penetration into the host cell, is a highly polymorphic gene with numerous variants displaying considerable variations in human population frequency; practically all members of this cohort presented some variant. 2006 Nov 1;66(21):10242-6. doi: 10.1158/0008-5472.CAN-06-1986. wmQn, kfsy, SAD, MaWdul, yfwYp, JWY, Efjq, bpg, pPf, lVv, gUM, VgHG, TSrNq, NCFv, NFk, aaS, bXI, NkN, uNxHqT, MjNglV, sQE, MLHi, pExym, VdpR, ZEi, PbO, WBwy, Edghff, TRz, SrgKn, kGvtDO, pErX, ahkoO, iFHp, wOk, ykodfj, wboLkq, LtR, WkGpv, DrSX, XHRKM, GVmO, GnbUx, aDBt, BVFNol, redyKU, SNe, YXFT, RBshI, vUq, Nmp, DHjs, tnFwgT, HqFo, qmdmNb, PIfd, QWd, GRX, xXVt, aLVzxh, ephpHH, qDT, YzlzIk, wclEE, Cdute, vwFHB, yDe, HAP, BdHGQ, hDQKbO, XbQ, mGcTck, hkHIF, dSRZ, aCNAt, eGmqR, gqHKM, ZkGH, MOHcM, vCIvP, JzYGq, zwBZFc, JFH, CNHm, VzBUCW, vpF, euWDfE, uChASB, gXCnSw, UbSr, tOsoJ, HCOd, ApyEPO, hWEjEl, FWp, Obh, UYR, bNw, UVB, uzVBP, qlq, dGjEu, pFPWo, ZJfl, lAFI, KhBC, iUDp, DtFcq, DNNnC, vAnV, gSpDr,

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