Heterogeneous expression of ACE2, TMPRSS2, and FURIN at single-cell resolution in advanced non-small cell lung cancer

Purpose Considering the high susceptibility of patients with advanced non-small cell lung cancer (NSCLC) to COVID-19, we explored the susceptible cell types and potential routes of SARS-CoV-2 infection in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by analyzing the expression patterns of the entry receptor angiotensin converting enzyme 2 ( ACE2 ) and the spike (S) protein priming proteases transmembrane serine protease 2 ( TMPRSS2 ) and FURIN . Methods Single-cell transcriptomic analysis of 14 LUSC and 12 LUAD samples was utilized to exhibit the heterogeneous expression of ACE2 , TMPRSS2 and FURIN across different cell subsets and individuals. Results 12 cell types and 33 cell clusters were identified from 26 cancer samples. ACE2 , TMPRSS2 and FURIN were heterogeneously expressed across different patients. Among all cell types, ACE2 , TMPRSS2 and FURIN were predominately expressed in cancer cells and alveolar cells, and lowly uncovered in other cells. Compared to LUSC, the protein priming proteases ( TMPRSS2 and FURIN ) were highly found in LUAD samples. However, ACE2 was not differentially expressed in cancer cells between the two cancer types. Moreover, ACE2 , TMPRSS2 , and FURIN expressions were not higher in any cell type of smokers than non-smokers. Conclusion Our research first revealed the heterogeneous expression of ACE2 , TMPRSS2 , and FURIN in different cell subsets of NSCLC and also across different individuals. These results provide insight into the specific cells targeted by SARS-CoV-2 (i.e., cancer cells and alveolar cells) in patients with advanced NSCLC, and indicate that smoking may be not an independent risk factor for NSCLC combined with COVID-19.