{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:10Z","timestamp":1792787650429,"version":"4.5.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Haiyan Science Foundation of Harbin Medical University Cancer Hospital","award":["JJYQ2024-07 and JJJQ2024-01"],"award-info":[{"award-number":["JJYQ2024-07 and JJJQ2024-01"]}],"id":[{"id":"https:\/\/ror.org\/01f77gp95","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["PL2024H171"],"award-info":[{"award-number":["PL2024H171"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303616"],"award-info":[{"award-number":["82303616"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Climbing Fund of Harbin Medical University Cancer Hospital","award":["PDTS2024A-05"],"award-info":[{"award-number":["PDTS2024A-05"]}],"id":[{"id":"https:\/\/ror.org\/01f77gp95","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Individualized and precise treatment of lung cancer","award":["Nn10py2017-04"],"award-info":[{"award-number":["Nn10py2017-04"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Lung cancer is the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma representing the predominant subtype. The increasing incidence of lung adenocarcinoma underscores the urgent need to establish novel therapeutic targets for clinical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed Mendelian randomization and colocalization analyses on large-scale lung adenocarcinoma genome-wide association study datasets. Bulk transcriptome and single-cell RNA sequencing were further applied to explore the function of candidate targets and related cell types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mendelian randomization revealed that elevated\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      expression causally reduced the risk of lung adenocarcinoma (odds ratio\u2009=\u20090.817, 95% confidence interval: 0.754\u20130.885,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001), whereas increased\n                      <jats:italic toggle=\"yes\">BTN3A2<\/jats:italic>\n                      expression was associated with an elevated disease risk. Colocalization analysis supported a shared causal variant between\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      and lung adenocarcinoma (posterior probability of hypothesis 4\u2009=\u200978.6%). Bulk transcriptome data demonstrated that\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      was upregulated in tumor tissues and was associated with better prognosis. Single-cell RNA sequencing revealed that macrophages were the predominant cell type expressing\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      , whereas weak expression was also detected in pulmonary epithelial cells and several other cell populations. There was a trend toward reduced abundance of high\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      -expressing macrophage subcluster 0 in tumor tissues, whereas low\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      -expressing subcluster 8 tended to accumulate within tumor lesions. Enrichment analysis of their signature genes suggested opposing biological roles in lung adenocarcinoma progression, which warrants further functional verification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      is closely associated with the occurrence and prognosis of lung adenocarcinoma. Macrophage-expressed\n                      <jats:italic toggle=\"yes\">RNASET2<\/jats:italic>\n                      represent a promising candidate molecule for further therapeutic exploration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605261488089","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:53:43Z","timestamp":1790150023000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiomics analysis identifies\n                    <i>RNASET2<\/i>\n                    as a potential candidate target associated with lung adenocarcinoma"],"prefix":"10.1177","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2257-7529","authenticated-orcid":false,"given":"Yue","family":"Shi","sequence":"first","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiankun","family":"Yang","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Cai","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Huang","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Bi","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyou","family":"Wang","sequence":"additional","affiliation":[{"name":"Harbin Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglong","family":"Kong","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoguo","family":"Lang","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shidong","family":"Xu","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Xu","sequence":"additional","affiliation":[{"name":"Harbin Medical University Cancer Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2204.0023"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33326-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2019.10.001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2018.12.006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106269"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01029-8"},{"key":"e_1_3_2_9_2","article-title":"Biological and therapeutic implications of the cancer-related germline mutation landscape in lung cancer","author":"Panagiotou E","unstructured":"Panagiotou E, Vathiotis IA, Makrythanasis P, et al. 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