tetano
Editor, Senior Moderator
Cell Transplant
. Jan-Dec 2020;29:963689720968749.
doi: 10.1177/0963689720968749.
ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients
Sara Ravaioli[SUP] 1 [/SUP], Michela Tebaldi[SUP] 2 [/SUP], Eugenio Fonzi[SUP] 2 [/SUP], Davide Angeli[SUP] 2 [/SUP], Massimiliano Mazza[SUP] 3 [/SUP], Fabio Nicolini[SUP] 3 [/SUP], Alessandro Lucchesi[SUP] 4 [/SUP], Francesca Fanini[SUP] 1 [/SUP], Francesca Pirini[SUP] 1 [/SUP], Maria Maddalena Tumedei[SUP] 1 [/SUP], Claudio Cerchione[SUP] 4 [/SUP], Pierluigi Viale[SUP] 5 [/SUP], Vittorio Sambri[SUP] 6 7 [/SUP], Giovanni Martinelli[SUP] 8 [/SUP], Sara Bravaccini[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. One open question is whether genetics could influence the severity of symptoms. Considering the limited data on cancer patients, we analyzed public data repositories limited to investigate angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) expressions and genetic variants to identify the basis of individual susceptibility to SARS-CoV-2.Gene expression and variant data were retrieved from Tissue Cancer Genome Atlas, Genotype-Tissue Expression, and gnomAD. Differences in gene expression were tested with Mann-Whitney U-test. Allele frequencies of germline variants were explored in different ethnicities, with a special focus on ACE2 variants located in the binding site to SARS-CoV-2 spike protein.The analysis of ACE2 and TMPRSS2 expressions in healthy tissues showed a higher expression in the age class 20 to 59 years (false discovery rate [FDR] < 0.0001) regardless of gender. ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR < 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR < 0.0001, respectively). ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR < 0.0001). Variants were present at low frequency (range 0% to 3%) and among those with the highest frequency, the variant S19P belongs to the SARS-CoV-2 spike protein binding site and it was exclusively present in Africans with a frequency of 0.2%.The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients.Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19.
Keywords: ACE2; SARS-CoV-2; TMPRSS2; individual susceptibility.
. Jan-Dec 2020;29:963689720968749.
doi: 10.1177/0963689720968749.
ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients
Sara Ravaioli[SUP] 1 [/SUP], Michela Tebaldi[SUP] 2 [/SUP], Eugenio Fonzi[SUP] 2 [/SUP], Davide Angeli[SUP] 2 [/SUP], Massimiliano Mazza[SUP] 3 [/SUP], Fabio Nicolini[SUP] 3 [/SUP], Alessandro Lucchesi[SUP] 4 [/SUP], Francesca Fanini[SUP] 1 [/SUP], Francesca Pirini[SUP] 1 [/SUP], Maria Maddalena Tumedei[SUP] 1 [/SUP], Claudio Cerchione[SUP] 4 [/SUP], Pierluigi Viale[SUP] 5 [/SUP], Vittorio Sambri[SUP] 6 7 [/SUP], Giovanni Martinelli[SUP] 8 [/SUP], Sara Bravaccini[SUP] 1 [/SUP]
Affiliations
- PMID: 33108902
- DOI: 10.1177/0963689720968749
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. One open question is whether genetics could influence the severity of symptoms. Considering the limited data on cancer patients, we analyzed public data repositories limited to investigate angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) expressions and genetic variants to identify the basis of individual susceptibility to SARS-CoV-2.Gene expression and variant data were retrieved from Tissue Cancer Genome Atlas, Genotype-Tissue Expression, and gnomAD. Differences in gene expression were tested with Mann-Whitney U-test. Allele frequencies of germline variants were explored in different ethnicities, with a special focus on ACE2 variants located in the binding site to SARS-CoV-2 spike protein.The analysis of ACE2 and TMPRSS2 expressions in healthy tissues showed a higher expression in the age class 20 to 59 years (false discovery rate [FDR] < 0.0001) regardless of gender. ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR < 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR < 0.0001, respectively). ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR < 0.0001). Variants were present at low frequency (range 0% to 3%) and among those with the highest frequency, the variant S19P belongs to the SARS-CoV-2 spike protein binding site and it was exclusively present in Africans with a frequency of 0.2%.The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients.Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19.
Keywords: ACE2; SARS-CoV-2; TMPRSS2; individual susceptibility.