The impact of ACE2 and co‐factors on SARS‐CoV‐2 infection in colorectal cancer

SARS-CoV-2 is the novel coronavirus leading to COVID19.1 Patients with cancer show a higher risk of infection with SARS-CoV-2 than patients without cancer.2,3 ACE24 and two co-factors, TMPRSS2 and FURIN,5,6 could be differentially expressed in various tissues involved in the susceptibility of cancer patients to SARS-CoV-2 infection. However, the functional role of these genes in colorectal cancer with COVID-19 is not clear. This study is the first report to explore the expression pattern of ACE2 and its co-factors in colorectal cancer, as well as their effects on SARS-CoV-2 infection. To assess the mRNA and protein levels of ACE2 and two co-factors in colorectal cancer, we performed RNAsequencing and proteomics analysis in both colorectal cancer tissues and adjacent normal tissues. ACE2 was higher in colorectal tumour tissues than in normal tissues (Figure 1A–C), whereas TMPRSS2 and FURIN were lower in tumour tissues compared to normal tissues (Figure 1D–H). The mRNA levels of TMPRSS2 and FURIN gradually decreased with malignant progression in the course of normal, adenoma, and tumour (Figure 1I–L). However, no significant increase in ACE2 mRNA was observed during malignant progression (Figure S1). The mRNA level of ACE2 positively correlated with TMPRRS2 and negatively correlated with FURIN (Figure S2). Stratification analysis showed that no significant differences in the age of onset, tumour site, or stage were related to the expression of these three genes (Figure S3). Based on single-cell RNA-sequencing profiling, ACE2 was primarily expressed in enterocyte cells (Figures 1M–R and S4). TMPRSS2 was primarily expressed in enterocytes and Paneth cells, and FURIN was expressed in all types of colorectal epithelial cells (Figure 1M–R). These results provide the co-expression pattern of ACE2 with its co-factors in colorectal tissues. Due to the low mRNA and protein expressions of ACE2 in colon cells (Figure S5A and Table S1), we constructed colon cells with a stable overexpression of ACE2