Transmembrane serine protease 2 is a prognostic factor for lung adenocarcinoma

Abstract

Transmembrane serine protease 2 (TMPRSS2) has been intensively investigated during the current Sars-CoV-2 pandemic as a virus activating protease. Furthermore, TMPRSS2 is an oncogenic gene associated with several cancer entities. Co-expression of TMPRSS2 and serpin family A member 1 (SERPINA1) (encoding alpha-1-antitrypsin; AAT) has been reported in the human lung. Recently, AAT was identified as a novel TMPRSS2 inhibitor. We previously reported that lower SERPINA1 expression in tumor tissues and higher levels of plasma AAT are associated with worse survival of patients with non-small cell lung cancer (NSCLC).In the present study, we sought to examine TMPRSS2 and SERPINA1/AAT expression in tumor and adjacent lung tissues from 347 NSCLC patients. Based on clinical data and gene expression analysis, we performed Cox regression for the survival analysis, and correlated TMPRSS2 and AAT protein levels in tissue samples by immunohistochemical and western blot analyses. We found that lower TMPRSS2 expression in tumor compared to adjacent non-tumor tissues is linked to a poor overall survival in patients with adenocarcinoma (ADC) and those who are current smokers. IHC staining of TMPRSS2 validated our findings in regard to overall survival while we did not observe a correlation with AAT staining. Based on western blot analyses, we found only a slight negative correlation between full-length TMPRSS2 and AAT in non-tumor tissues, which seems to be related to smoking status. Taken together, we demonstrated that TMPRSS2 is a prognostic factor in patients with lung ADC; however, a link between AAT and TMPRSS2 proteins warrants further investigation.

PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18 pathway

“…TMPRSS2 is associated with the development of prostate cancer and the promotion of SARS‐CoV‐2 infection of lung cells (Hoffmann et al , 2020 ). However, the biological function of TMPRSS2 in lung cancer is unclear, and the current research results are inconsistent (Wang et al , 2021 ; Schneider et al , 2022 ). To determine whether the expression level of TMPRSS2 is increased in lung cancer cells, we examined the endogenous protein level of TMPRSS2 in four established lung cancer cell lines and two normal lung fibroblasts by Western blotting.…”

In Vitro Evidence of Statins’ Protective Role against COVID-19 Hallmarks

“…However, prolonged time of treatment (48 h), with the highest concentrations of ATS (5 µM) and PVS (20 µM), produced a slight but not significant decrease of TMPRSS2 ( Figure 1 A,C). Interestingly, Western blot analysis allows us to detect an additional band of about 32 kDa which, based on the literature, corresponds to serine protease catalytic domain, directly involved in cell surface protein interaction, which is a product of auto-cleavage [ 31 , 32 , 33 ]. In this model, the cleaved domain of TMPRSS2 results in significant downregulation starting from 24 h of treatments with both the compounds and prolonged after 48 h in a dose-dependent manner ( Figure 1 A,C).…”

Impact of SARS-CoV-2 Spike Mutations on Its Activation by TMPRSS2 and the Alternative TMPRSS13 Protease

“…In the case of TMPRSS2, the polyclonal antibody detected two specific bands besides a few aspecific products. The band of ~55 kDa represents full-length TMPRSS2 ( 30 ), while that of ~32 kDa represents the serine protease domain resulting from autocleavage. For TMPRSS13, we observed two dominant bands: full-length TMPRSS13 having, in glycosylated form, a molecular weight (MW) of ~70 kDa and the presumed intracellular fragment of ~26 kDa that results from autocleavage ( 31 ).…”