{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:59:05Z","timestamp":1777510745466,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:p>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.<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>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] &lt; 0.0001) regardless of gender. ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR &lt; 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR &lt; 0.0001, respectively). ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR &lt; 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%.<\/jats:p>\n                  <jats:p>The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients.<\/jats:p>\n                  <jats:p>Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19.<\/jats:p>","DOI":"10.1177\/0963689720968749","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T01:27:32Z","timestamp":1603848452000},"page":"096368972096874","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients"],"prefix":"10.1177","volume":"29","author":[{"given":"Sara","family":"Ravaioli","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0717-2748","authenticated-orcid":false,"given":"Michela","family":"Tebaldi","sequence":"additional","affiliation":[{"name":"Department of Research and Innovation, Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio","family":"Fonzi","sequence":"additional","affiliation":[{"name":"Department of Research and Innovation, Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Angeli","sequence":"additional","affiliation":[{"name":"Department of Research and Innovation, Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"Mazza","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Immunotherapy, Cell Therapy and Biobank (ITCB), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Nicolini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Immunotherapy, Cell Therapy and Biobank (ITCB), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Lucchesi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Fanini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Pirini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Maddalena","family":"Tumedei","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Cerchione","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierluigi","family":"Viale","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Sambri","sequence":"additional","affiliation":[{"name":"Unit of Microbiology, The Great Romagna Area Hub Laboratory, Pievesestina, Cesena, Italy"},{"name":"Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Scientific Directorate, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-8538","authenticated-orcid":false,"given":"Sara","family":"Bravaccini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental oncology and hematology, Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"bibr1-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2020-0213"},{"key":"bibr2-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30230-8"},{"key":"bibr3-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30096-6"},{"issue":"18","key":"bibr4-0963689720968749","first-page":"1775","volume":"323","author":"Onder G","year":"2020","journal-title":"JAMA"},{"key":"bibr5-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30117-X"},{"key":"bibr6-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22849"},{"key":"bibr7-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1111\/all.14344"},{"key":"bibr8-0963689720968749","author":"Zhao J","journal-title":"medRxiv"},{"key":"bibr9-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00510-20"},{"key":"bibr10-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.045"},{"key":"bibr11-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1038\/nature02145"},{"key":"bibr12-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116480"},{"key":"bibr13-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600640"},{"key":"bibr14-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02232-10"},{"key":"bibr15-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01542-10"},{"key":"bibr16-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02062-10"},{"key":"bibr17-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1038\/nature12711"},{"key":"bibr18-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072942"},{"key":"bibr19-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01774-19"},{"key":"bibr20-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-2-69"},{"key":"bibr21-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1093\/function\/zqaa012"},{"key":"bibr22-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-020-02383-3"},{"key":"bibr23-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1126\/science.1262110"},{"issue":"1","key":"bibr24-0963689720968749","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Hochberg Y","year":"1995","journal-title":"J R Stat Soc Ser B"},{"key":"bibr25-0963689720968749","first-page":"92","author":"Perktold J","year":"2010","journal-title":"PROC. 9th PYTHON Sci. CONF"},{"key":"bibr26-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"bibr27-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25832"},{"key":"bibr28-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"bibr29-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1200\/GO.20.00097"},{"key":"bibr30-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.04.001"},{"key":"bibr31-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2020.05.001"},{"key":"bibr32-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.02.055"},{"key":"bibr33-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-020-00973-x"},{"key":"bibr34-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.02.054"},{"key":"bibr35-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01209-2"},{"key":"bibr36-0963689720968749","author":"Ma L","journal-title":"medRxiv"},{"key":"bibr37-0963689720968749","author":"Wambier C","year":"2020","journal-title":"Res Gate"},{"key":"bibr38-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.04.032"},{"key":"bibr39-0963689720968749","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.13455"},{"key":"bibr40-0963689720968749","doi-asserted-by":"publisher","DOI":"10.3390\/v2020574"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0963689720968749","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0963689720968749","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0963689720968749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:38:18Z","timestamp":1777390698000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.sagepub.com\/doi\/10.1177\/0963689720968749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":40,"alternative-id":["10.1177\/0963689720968749"],"URL":"https:\/\/doi.org\/10.1177\/0963689720968749","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,1]]}}}