A Comprehensive Analysis of NRP1 in Malignancies Provide Therapeutic Implication for Treating Cancer Patients Infected with SARS-CoV-2

Abstract

COVID-19 (Coronavirus disease 2019) is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which can lead to pneumonia, cytokine storms, and lymphopenia. Patients with cancer are more susceptible to SARS-CoV-2 infection and severe COVID-19 due to immunosuppression. Recent studies have indicated that NRP1 (Neuropilin 1) may act as a novel mediator of SARS-CoV-2 entry into the host cell. As no systematic review has been performed investigating the characteristics of NRP1 in pan-carcinoma, we comprehensively analyzed NRP1 in patients with pan-cancer. Using a bioinformatics approach, we aimed to systematically examine NRP1 expression profiles in both pan-carcinoma and healthy tissues. We found that lung and genitourinary cancers have a relatively higher NRP-1 expression than other cancer patients, suggesting that these patients may be more susceptible to SARS-CoV-2. Our analysis further revealed that NRP1 expression was downregulated in Vero E6 cells, whole blood, lung organoids, testis tissue, and alveolospheres infected with SARS-CoV-2. Notably, NRP1 was associated with immune cell infiltration, immune checkpoint genes, and immune-related genes in most patients with cancer. These findings suggest that, in patients with specific types of cancer, especially lung and genitourinary, high expression of NRP1 contributes to greater susceptibility to SARS-CoV-2 infection and an increased risk of damage due to cytokine storms. Overall, NRP1 appears to play a critical role in regulating immunological properties and metabolism in many tumor types. Specific inhibitors of the NRP1 antigen (pegaptanib, EG00229, or MNRP1685A) combined with other anti-SARS-CoV-2 strategies may aid in treating patients with lung and genitourinary cancers following SARS-CoV-2 infection.