{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T10:29:17Z","timestamp":1764584957890,"version":"3.46.0"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014294","name":"Kentucky Humanities Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014294","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17KK0177"],"award-info":[{"award-number":["17KK0177"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Actinin\u20104 (gene name:\n                    <jats:italic>ACTN4<\/jats:italic>\n                    ) is an actin\u2010bundling protein implicated in cancer invasion and metastasis. This study evaluated whether\n                    <jats:italic>ACTN4<\/jats:italic>\n                    amplification and actinin\u20104 protein expression were associated with osimertinib efficacy in epidermal growth factor receptor\u2010mutant non\u2010small cell lung cancer. We retrospectively analyzed 63 patients with epidermal growth factor receptor\u2010mutant non\u2010small cell lung cancer treated with osimertinib as first\u2010line treatment. Immunohistochemistry was performed for pretreatment tumor tissues. Actinin\u20104 immunohistochemistry positivity was defined as positive staining of\u2009\u2265\u200930% tumor cells. In positive cases,\n                    <jats:italic>ACTN4<\/jats:italic>\n                    amplification was assessed via fluorescence in\u00a0situ hybridization. Progression\u2010free survival and overall survival were compared across groups. Among 63 patients (median age: 73\u2009years, 52 with Eastern Cooperative Oncology Group performance status 0\u20131, 63 with adenocarcinoma; epidermal growth factor receptor mutations: 19del\/L858R\/uncommon\u2009=\u200932\/24\/7), there were 33 and 30 actinin\u20104 immunohistochemistry\u2010positive and actinin\u20104 immunohistochemistry\u2010negative cases, respectively. The propensity score\u2010weighted overall survival and progression\u2010free survival were significantly shorter for actinin\u20104 immunohistochemistry\u2010positive patients than for actinin\u20104 immunohistochemistry\u2010negative patients (overall survival: hazard ratio, 2.76; 95% confidence interval, 1.02\u20137.45; progression\u2010free survival: hazard ratio, 1.91; 95% confidence interval, 1.03\u20133.54). Among the 33 actinin\u20104 immunohistochemistry\u2010positive cases, four showed positivity in\n                    <jats:italic>ACTN4<\/jats:italic>\n                    fluorescence in\u00a0situ hybridization. Overall survival and progression\u2010free survival were numerically shorter for patients with\n                    <jats:italic>ACTN4<\/jats:italic>\n                    positivity than for those with\n                    <jats:italic>ACTN4<\/jats:italic>\n                    negativity in fluorescence in\u00a0situ hybridization. The findings suggest that\n                    <jats:italic>ACTN4<\/jats:italic>\n                    amplification and actinin\u20104 protein expression are prognostic markers for poor osimertinib efficacy in epidermal growth factor receptor\u2010mutant non\u2010small cell lung cancer.\n                  <\/jats:p>","DOI":"10.1111\/cas.70209","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T04:40:37Z","timestamp":1760157637000},"page":"3367-3375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>ACTN4<\/i>\n                    <\/scp>\n                    Gene Amplification and Actinin\u20104 Protein Expression for Osimertinib Efficacy in\n                    <scp>\n                      <i>EGFR<\/i>\n                    <\/scp>\n                    \u2010Mutant\n                    <scp>NSCLC<\/scp>"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3774-8915","authenticated-orcid":false,"given":"Takehiro","family":"Tozuka","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4912-4138","authenticated-orcid":false,"given":"Rintaro","family":"Noro","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-601X","authenticated-orcid":false,"given":"Yutaka","family":"Naito","sequence":"additional","affiliation":[{"name":"Division of Bioregulation, Institute for Advanced Medical Science Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nami","family":"Miura","sequence":"additional","affiliation":[{"name":"Division of Bioregulation, Institute for Advanced Medical Science Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Kunugi","sequence":"additional","affiliation":[{"name":"Department of Analytic Human Pathology Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1321-5345","authenticated-orcid":false,"given":"Kazufumi","family":"Honda","sequence":"additional","affiliation":[{"name":"Division of Bioregulation, Institute for Advanced Medical Science Nippon Medical School  Tokyo Japan"},{"name":"Department of Bioregulation, Graduate School of Medicine Nippon Medical School  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Seike","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Oncology Graduate School of Medicine, Nippon Medical School  Tokyo 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