Colon Cancer and SARS-CoV-2: Impact of ACE2 Expression in Susceptibility to COVID-19

Abstract

Novel coronavirus disease (COVID-19) pandemic has become a global health emergency. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with angiotensin-converting enzyme 2 (ACE2) to enter the cells and infects diverse human tissues. It has been reported that a few conditions, including cancer, predispose individuals to SARS-CoV-2 infection and severe form of COVID-19. These findings led us to evaluate the susceptibility of colon adenocarcinoma (COAD) patients to SARS-CoV-2 infection by investigation of ACE2 expression in their tumor tissues. The expression analysis revealed that both mRNA and protein levels of ACE2 had increased in colon cancer samples than normal group. Next, the prognosis analysis has indicated that the upregulation of ACE2 was not correlated with patient survival outcomes. Further assessment displayed the hypomethylation of the ACE2 gene promoter in COAD patients. Surprisingly, this methylation status has a strong negative correlation with ACE2 gene expression. The functional enrichment analysis of the genes that had similar expression patterns with ACE2 in colon cancer tissues demonstrated that they mainly enriched in Vitamin digestion and absorption, Sulfur relay system, and Fat digestion and absorption pathways. Finally, we found that ACE2 gene expression had a significant association with the immune cell infiltration levels in COAD patients. In conclusion, it has plausible that COAD patients are more likely to be infected with SARS-CoV-2 and experience severe injuries. Moreover, COVID-19 would bring unfavorable survival outcomes of patients with colon cancer by the way of immune cell infiltration linked process. The present study highlights the importance of preventive actions for COAD patients during the COVID-19 pandemic.

Anosmia: a missing link in the neuroimmunology of coronavirus disease 2019 (COVID-19)

“…More than 80% of people have shown mild to moderate infection, while the remaining portion would progress to severe and critical conditions. Older people and people with comorbidity, especially cardiovascular disease, diabetes, mostly make up the population of those dying from COVID-19 (Ahmadi et al 2020;Hessami et al 2020;Shamshirian and Rezaei 2020;Sahu et al 2020). However, the observation of severe infection and death from infection in young people and people without a preexisting condition has pointed to the possible role of genetics in susceptibility to COVID-19 (Ahanchian et al 2020;Darbeheshti and Rezaei 2020;Yousefzadegan and Rezaei 2020).…”

Cancerona: Challenges of Cancer Management in Times of COVID-19 Pandemic

“…Further assessment showed that the ACE2 gene promoter is hypomethylated in COAD patients and the methylation status is negatively correlated with ACE2 expression. On the other hand, ACE2 gene expression positively correlated with infiltration level of immune cells including memory B cell, plasma B cell, activated myeloid dendritic cell, and resting myeloid dendritic cell in COAD patients [59]. SARS-CoV-2 infection was shown to reduce ACE2 level post-infection [58], which would bring poor prognosis for patients with colon cancer due to altered immune cell infiltration level.…”

“…Analyzing the expression of ACE2 in various tumor tissues has been also used to evaluate the susceptibility of these patients to SARS-CoV-2 infection. Ahmadi et al [59] showed that ACE2 mRNA and protein levels were higher in colon adenocarcinoma (COAD) patients than in the control group, suggesting more susceptibility to COVID-19. This upregulation was not correlated with patient survival outcomes.…”

Upregulation of PD‐L1 by SARS‐CoV‐2 promotes immune evasion

“…Cancer patients are more susceptible to SARS-CoV-2 and are more likely to develop severe COVID-19. 84,85 It remains unclear if anti-PD-1/PD-L1 treatment would be beneficial for COVID-19 patients. Immune checkpoint inhibitors (ICI) may enhance the cytokine storm associated with higher COVID-19 morbidity and mortality.…”