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ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients.
Cell Transplant. 2020 Jan-Dec; 29:963689720968749.CT

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.

Authors+Show Affiliations

Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Research and Innovation, Unit of Biostatistics and Clinical Trials, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Research and Innovation, Unit of Biostatistics and Clinical Trials, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Research and Innovation, Unit of Biostatistics and Clinical Trials, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Immunotherapy, Cell Therapy and Biobank (ITCB), 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Immunotherapy, Cell Therapy and Biobank (ITCB), 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Hematology Unit, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Hematology Unit, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Infectious Diseases Unit, Department of Medical and Surgical Sciences, 9296Alma Mater Studiorum University of Bologna, Bologna, Italy.Unit of Microbiology, The Great Romagna Area Hub Laboratory, Pievesestina, Cesena, Italy. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.Scientific Directorate, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, 124882Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33108902

Citation

Ravaioli, Sara, et al. "ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients." Cell Transplantation, vol. 29, 2020, p. 963689720968749.
Ravaioli S, Tebaldi M, Fonzi E, et al. ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients. Cell Transplant. 2020;29:963689720968749.
Ravaioli, S., Tebaldi, M., Fonzi, E., Angeli, D., Mazza, M., Nicolini, F., Lucchesi, A., Fanini, F., Pirini, F., Tumedei, M. M., Cerchione, C., Viale, P., Sambri, V., Martinelli, G., & Bravaccini, S. (2020). ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients. Cell Transplantation, 29, 963689720968749. https://doi.org/10.1177/0963689720968749
Ravaioli S, et al. ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients. Cell Transplant. 2020 Jan-Dec;29:963689720968749. PubMed PMID: 33108902.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients. AU - Ravaioli,Sara, AU - Tebaldi,Michela, AU - Fonzi,Eugenio, AU - Angeli,Davide, AU - Mazza,Massimiliano, AU - Nicolini,Fabio, AU - Lucchesi,Alessandro, AU - Fanini,Francesca, AU - Pirini,Francesca, AU - Tumedei,Maria Maddalena, AU - Cerchione,Claudio, AU - Viale,Pierluigi, AU - Sambri,Vittorio, AU - Martinelli,Giovanni, AU - Bravaccini,Sara, PY - 2020/10/28/entrez PY - 2020/10/29/pubmed PY - 2020/11/5/medline KW - ACE2 KW - SARS-CoV-2 KW - TMPRSS2 KW - individual susceptibility SP - 963689720968749 EP - 963689720968749 JF - Cell transplantation JO - Cell Transplant VL - 29 N2 - 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. SN - 1555-3892 UR - https://www.unboundmedicine.com/medline/citation/33108902/ACE2_and_TMPRSS2_Potential_Involvement_in_Genetic_Susceptibility_to_SARS_COV_2_in_Cancer_Patients_ L2 - https://journals.sagepub.com/doi/10.1177/0963689720968749?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -