{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:44:37Z","timestamp":1772163877266,"version":"3.50.1"},"reference-count":55,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T00:00:00Z","timestamp":1594771200000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["Department of Defense Career Development Award (W8"],"award-info":[{"award-number":["Department of Defense Career Development Award (W8"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Arthur J Schreiner Family Melanoma Research","award":["Arthur J Schreiner Family Melanoma Research Fund"],"award-info":[{"award-number":["Arthur J Schreiner Family Melanoma Research Fund"]}]},{"name":"J. Edward Mahoney Foundation","award":["J. Edward Mahoney Foundation Research Fund"],"award-info":[{"award-number":["J. Edward Mahoney Foundation Research Fund"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. Modestly sized case series have described clinical factors associated with COVID-19, while\n                      <jats:italic>ACE2<\/jats:italic>\n                      and\n                      <jats:italic>TMPRSS2<\/jats:italic>\n                      expression analyses have been described in some cell types. Patients with cancer may have worse outcomes to COVID-19.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed an integrated study of\n                      <jats:italic>ACE2<\/jats:italic>\n                      and\n                      <jats:italic>TMPRSS2<\/jats:italic>\n                      gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). We correlated gene expression with clinical factors (including but not limited to age, gender, race, body mass index, and smoking history), HLA genotype, immune gene expression patterns, cell subsets, and single-cell sequencing as well as commensal microbiome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Matched normal tissues generally display higher\n                      <jats:italic>ACE2<\/jats:italic>\n                      and\n                      <jats:italic>TMPRSS2<\/jats:italic>\n                      expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. No clinical factors were consistently identified to be significantly associated with gene expression levels though outlier organ systems were observed for some factors. Similarly, no HLA genotypes were consistently associated with gene expression levels. Strong correlations were observed between\n                      <jats:italic>ACE2<\/jats:italic>\n                      expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-\u03b2 signatures.\n                      <jats:italic>ACE2<\/jats:italic>\n                      positively correlated with macrophage subsets across tumor types.\n                      <jats:italic>TMPRSS2<\/jats:italic>\n                      was less associated with immune gene expression but was strongly associated with epithelial cell abundance. Single-cell sequencing analysis across nine independent studies demonstrated little to no\n                      <jats:italic>ACE2<\/jats:italic>\n                      or\n                      <jats:italic>TMPRSS2<\/jats:italic>\n                      expression in lymphocytes or macrophages.\n                      <jats:italic>ACE2<\/jats:italic>\n                      and\n                      <jats:italic>TMPRSS2<\/jats:italic>\n                      gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We performed a large-scale integration of\n                      <jats:italic>ACE2<\/jats:italic>\n                      and\n                      <jats:italic>TMPRSS2<\/jats:italic>\n                      gene expression across clinical, genetic, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We suggest caution in interpretation regarding genetic associations with\n                      <jats:italic>ACE2<\/jats:italic>\n                      expression suggested from smaller case series.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2020-001020","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T06:55:29Z","timestamp":1594882529000},"page":"e001020","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["<i>ACE2<\/i>\n                    and\n                    <i>TMPRSS2<\/i>\n                    expression by clinical, HLA, immune, and microbial correlates across 34 human cancers and matched normal tissues: implications for SARS-CoV-2 COVID-19"],"prefix":"10.1136","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6105-1704","authenticated-orcid":false,"given":"Riyue","family":"Bao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-4908","authenticated-orcid":false,"given":"Jason John","family":"Luke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"2020071603552221000_8.2.e001020.1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2","volume":"5","year":"2020","journal-title":"Nat Microbiol"},{"key":"2020071603552221000_8.2.e001020.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)302518"},{"key":"2020071603552221000_8.2.e001020.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30185-9"},{"key":"2020071603552221000_8.2.e001020.4","unstructured":"Guan WJ , ZY N , Hu Y , et al . 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