(33) Recently, our research group has described that the transmembrane protease serine 4 (TMPRSS4) promoter region is often hypomethylated in ADC and SCC lung cancer subtypes compared with normal lung tissue, suggesting that the methylation levels of the TMPRSS4 promoter might be useful as a diagnostic tool in lung cancer.
Using ddPCR for the detection of DNA methylation in the TMPRSS4 promoter gene in bisulfite-converted samples, we were able to detect TMPRSS4 promoter hypomethylation with very low input of DNA, as low as 0.5 ng (3.3 copies/[micro]L; Figure 4).
Epigenetic alterations leading to TMPRSS4 promoter hypomethylation and protein overexpression predict poor prognosis in squamous lung cancer patients.
There are 8 out of 10 downregulated DEGs that are downregulated in Group II compared with those in Group I, namely VIPR1, SLC6A4, NECAB1, LEPREL1, ITLN2, HSD17B6, HHIP, and CRTAC1 and 14 out of 57 upregulated DEGs that are upregulated in Group II compared with those in Group I, namely TRIM2, TP63, TMPRSS4
, SPP1, SIX4, MMP1, ITGB8, GOLM1, CP, COL17A1, CLIC6, CDH3, CD24, and C12orf75.
Proteolytic activation of seasonal human IAV HA occurs extracellularly or on the cell membrane in the airway by trypsin-type proteases, such as tryptase Clara, (19) mini-plasmin, (7) trypsin, (3) ectopic pancreatic trypsin, (4),(8),(10),(11),(21) porcine lung tryp tase, (22) TC30 (23) and type-II membrane bound proteases, human airway trypsin-like protease (HAT), transmembrane serine protease (TMPRSS)2 (24) and TMPRSS4 (25) (Table 1).
As outlined in this review, the knowledge gained within the last decades and the experience gained from the pandemic influenza A (H1N1) 2009 and HPAI outbreak greatly improved our understanding of the role of host cellular factors in the pathogenicity of IAV infection: (i) Several cell surface anchored trypsin-like serine proteases are candidates of HA-processing protease for seasonal human IAV, TMPRSS2, HAT and TMPRSS4, other than secreted HA-processing proteases in the airway, such as tryptase Clara, trypsin and mini-plasmin, and for HPAI viruses MSPL/ TMPRSS13 other than furin and PCs.