Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread around the world and became a global pandemic in 2020. One promising drug target for SARS-CoV-2 is the transmembrane
protease serine 2 (TMPRSS2). This study was designed to explore the expression status, prognostic significance and molecular functions of TMPRSS2 in
lung cancer. TMPRSS2 expression was investigated using the TIMER, Oncomine, UALCAN, GEO, HPA and TCGA databases. The prognostic value of TMPRSS2 was examined using Cox regression and a nomogram. KEGG, GO and GSEA were performed to investigate the cellular function of TMPRSS2 in
lung cancer. The relationship between TMPRSS2 and immune infiltration was determined using the TIMER and CIBERSORT algorithms. TMPRSS2
mRNA and
protein expression was significantly reduced in
lung cancer. Decreased TMPRSS2 expression and increased DNA methylation of TMPRSS2 were associated with various clinicopathological parameters in patients with
lung cancer. Low TMPRSS2
mRNA expression also correlated with poor outcome in
lung cancer patients. Moreover, a nomogram was constructed and exhibited good predictive power for the overall survival of
lung cancer patients. KEGG and GO analyses and GSEA implied that multiple immune- and metabolism-related pathways were significantly linked with TMPRSS2 expression. Intriguingly, TMPRSS2 expression associated with immune cell infiltration in
lung cancer. More importantly, TMPRSS2 expression was markedly decreased in SARS-CoV-infected cells. These findings indicate that TMPRSS2 may be a promising prognostic
biomarker and therapeutic target for
lung cancer through metabolic pathways and immune cell infiltration.