TMPRSS2 Serves as a Prognostic Biomarker and Correlated With Immune Infiltrates in Breast Invasive Cancer and Lung Adenocarcinoma

Abstract

TMPRSS2 is a transmembrane serine protease and plays a pivotal role in coronavirus disease 2019 (COVID-19). However, the correlation of TMPRSS2 with prognosis and immune infiltration in tumors has not yet been explored. Here, we analyzed the expression of TMPRSS2 in Oncomine and TIMER databases, the correlation between TMPRSS2 and overall survival in the PrognoScan, Kaplan-Meier plotter, and GEPIA databases. The association between TMPRSS2 and immune infiltration levels was investigated in the TIMER database. In addition, the prognosis of TMPRSS2 related to immune cells in cancers was analyzed. Quantitative real-time PCR (qRT-PCR) confirmed that TMPRSS2 was upregulated in lung adenocarcinoma (LUAD) and downregulated in breast invasive carcinoma (BRCA). We demonstrated that high TMPRSS2 expression was associated with favorable prognosis in LUAD, but it was associated with poor prognosis in BRCA. Interestingly, we found that TMPRSS2 expression was significantly correlated with immune infiltration of B cells, CD4+ T cells, macrophages, and dendritic cells in LUAD, and it was positively correlated with the infiltrating levels of CD8+ T cells, CD4+ T cells, neutrophils, and dendric cells in BRCA. Consistent with the prognosis of TMPRSS2 in LUAD and BRCA, the high expression level of TMPRSS2 has a favorable prognosis in enriched immune cells such as B cells, macrophages, and CD4+ T cells in LUAD, and it has a poor prognosis in CD4+ T cells and CD8+ T cells in BRCA. In conclusion, our results indicate that the prognosis of TMPRSS2 in LUAD and BRCA is significantly correlated with immune cells infiltration. Our study comprehensively revealed the relationship between the prognosis of TMPRSS2 in pan-cancers and tumor immunity.

Artemisia argyi extracts overcome lapatinib resistance via enhancing TMPRSS2 activation in HER2‐positive breast cancer

“…58 The occurrence of the TMPRSS2-ERG fusion gene is influenced by hormonal factors, including dietary estrogens, 59 estrogen receptor alpha (ERα), 60 and androgen. 61 Consequently, the detrimental impact of the TMPRSS2-ERG fusion gene was also observed in ER-positive breast cancer, 62,63 leading to resistance to estrogen treatment. 64 Interestingly, Mice lacking Tmprss2 À/À without ERG expression had exhibited prostate cancer sizes over twice as large as those observed in Tmprss2 +/+ mice.…”

Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer

“…Thus, exploring the susceptibility to coronavirus and the physiological functions of TMPRSS2 in humans is essential to the ongoing global drive to manage this pandemic. Previous reports have suggested that patients with cancer are more susceptible to infections, and several bioinformatics analyses have shown that cancer tissues have higher TMPRSS2 expression levels than matched healthy tissues in lung and stomach cancer ( 24 , 25 ). As previously reported, patients with COVID-19 usually exhibit multi-organ damage, especially aerodigestive disease ( 26 ).…”

Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy

“…23.537985 doi: bioRxiv preprint overexpressed in different cancer types, notably prostate, invasive breast, head and neck cancers, and lung carcinoma, making it an attractive biomarker for the early diagnosis. [5][6][7] TMPRSS2 is related to carcinogenesis, cancer metastatic progression, 8,9 and its role on the chronic pain experienced by patients has also been stressed out. 10 Indeed, its localization at the surface of cancer cells allows the protein to mediate, via its proteolytic activity, different signaling cascades and transduction between the cells and the extracellular medium, including pain signals.…”