Impacts of transmembrane serine protease 4 expression on susceptibility to severe acute respiratory syndrome coronavirus 2

TMPRSS4 expression at both the transcriptional and translational level in human organs and tissues was presented in Supplementary Figure 1B, http://links.lww.com/CM9/B287, which shows that TMPRSS4 messenger ribonucleic acid (mRNA) was primarily expressed in the proximal digestive tract, kidney, urinary bladder, and gastrointestinal tract, then in the bone marrow, lymphoid tissues, reproductive organs, liver, gallbladder, and skin, whereas the distribution of TMPRSS4 protein was significantly distinct from the mRNA expression patterns. With the exception of the eyes, TMPRSS4 protein expression was generally observed in all organs and tissues, including the gastrointestinal tract and lungs, and the top four tissues for TMPRSS4 mRNA expression were the esophagus (proximal digestive tract), urinary bladder (kidney and urinary bladder), colon, and rectum (gastrointestinal tract) [Supplementary Figure 1C, http://links.lww.com/CM9/B287]. Additionally, two critical organs that are subject to SARS-CoV-2 attack are the lungs and pancreas, where tissue expression of TMPRSS4/TMPRSS2 was high. [...]we compared TMPRSS4 and TMPRSS2 expression in lung cancer and PAAD tissues with corresponding normal tissues using GEPIA 2 in The Cancer Genome Atlas (TCGA) database. According to these expression patterns, we concluded that TMPRSS4 may play more important roles than TMPRSS2 in SARS-CoV-2 entry into lung cancer and PAAD patients, while TMPRSS2 may be primarily responsible for SARS-CoV-2 attack in healthy people. Another nucleoside derivative of CD, m62A, was examined for its inhibitory effect on TMPRSS4 expression by Western blotting and RT-PCR [Supplementary File, http://links.lww.com/CM9/B287]. [...]both CD and m62A, and the small molecule TQ may have therapeutic potential as anti-SARS-CoV-2 agents by suppressing TMPRSS4 expression. [...]our work revealed the expression and distribution of TMPRSS4 in various tissues, and implied that the expression of TMPRSS4 has specific significance for prognosis across different cancer types.