Potential applications of prognostic and immunological marker transmembrane serine proteinase 2 in prediction, prevention and personalized treatment of lung cancer

Transmembrane serine proteinase 2 (TMPRSS2), which is an essential serine protease for priming spike protein of SARS-CoV-2, was found in low expression in many cancer tissue including lung cancer. However, the mechanism of severely downregulated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was not reported yet; the correlation between TMPRSS2 and prognosis in LUAD and LUSC is also not clear. In our present research, we found that TMPRSS2 was severely downregulated in LUAD and LUSC, and the expression of TMPRSS2 in LUAD is much lower than that of LUSC. Low TMPRSS2 expression was an independent prognostic factor for poor OS in LUAD, but not in LUSC patients. Promoter hypermethylation is one of the results of TMPRSS2 downregulated in LUAD and LUSC, whereas copy-number alteration is another reason for TMPRSS2 downregulated in LUAD but not LUSC. Then, low TMPRSS2 expression has higher prognostic value in LUAD and may be due to different immune environments and different enriched immune cells subgroups.