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High\n                      <jats:italic>PDLIM2<\/jats:italic>\n                      expression was linked to lower mutation rates in\n                      <jats:italic>RB1<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>SMARCA4, STK11<\/jats:italic>\n                      , and\n                      <jats:italic>KEAP1<\/jats:italic>\n                      , but increased\n                      <jats:italic>EGFR<\/jats:italic>\n                      mutations (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01).\n                      <jats:italic>PDLIM2<\/jats:italic>\n                      -high tumors also showed increased immune cell infiltration, T cell-inflamed scores, and PD-L1 positivity (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.008). High\n                      <jats:italic>PDLIM2<\/jats:italic>\n                      was associated with improved survival (24.1 vs 18.1 months;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, HR\u2009=\u20090.84) and remained prognostic in multivariate analysis (HR\u2009=\u20090.88, 95% CI 0.83\u20130.93), as well as with longer pembrolizumab time, especially with platinum-based therapy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012, HR\u2009=\u20090.867). In two LUAD mouse models, nanoPDLIM2 improved median overall survival versus chemoimmunotherapy alone (10\u201312.5 vs 8\u20139 days; N\u2009=\u20098;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001, 0.0003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>PDLIM2<\/jats:italic>\n                      is a promising prognostic biomarker in LUAD linked to immune-receptive tumors. Preclinically,\n                      <jats:italic>PDLIM2<\/jats:italic>\n                      -based therapy enhances chemoimmunotherapy efficacy, though its predictive role warrants further evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03570-3","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T14:52:10Z","timestamp":1786200730000},"page":"1686-1693","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring PDLIM2 as a prognostic biomarker and therapeutic target in lung adenocarcinoma"],"prefix":"10.1038","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1825-1033","authenticated-orcid":false,"given":"Karam","family":"Ashouri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-8031","authenticated-orcid":false,"given":"Andrew","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen V.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7548-8360","authenticated-orcid":false,"given":"Balazs","family":"Halmos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gutian","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Vanderwalde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1605-4719","authenticated-orcid":false,"given":"Jorge J.","family":"Nieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2769-9814","authenticated-orcid":false,"given":"Zhaoxia","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"3570_CR1","first-page":"10","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. 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AE and AV report employment and stock with Caris Life Sciences. PCM reports receiving consulting honorarium from AstraZeneca, BeiGene, Pfizer and Daiichi Sankyo; and conference traveling support from DAVA Oncology; and clinical trial research grants to the institution from Apollomics, BeiGene, AstraZeneca, OncoC4, GenMab, Elevation Oncology, Merck, AbbVie and Mirati. SVL reports research funding (to institution) from Abbvie, Alkermes, AstraZeneca, BioNTech, Bristol-Myers Squibb, Cogent Biosciences, Duality, Elevation Oncology, Ellipses, Genentech, Gilead, Medilink, Merck, Merus, Nuvalent, OSE Immunotherapeutics, Puma, RAPT, Synthekine, SystImmune; consulting fees from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Genentech\/Roche, Gilead, GSK, Guardant Health, Johnson & Johnson, Jazz Pharmaceuticals, Lilly, Merck, Merus, Mirati, Natera, Novartis, Nuvalent, OSE Immunotherapeutics, Pfizer, Regeneron, Revolution Medicines, Takeda, Yuhan. JNJ reports research funding from Merck and Genentech, Personal fees from Aadi Biosciences, ANP Technologies, Astra Zeneca, BioAtla, BMS, Catalym, G1 Therapeutics, Gilead, Genentech, Kalivir, Mindmed, Naveris, Sanofi Tubulis, Urogen. Ownership interests in Affyimmune, Cansera, Indee Bio, Quantgene, Amgen, Johnson & Johnson, Novartis. All remaining authors have declared no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This study was conducted in accordance with guidelines of the Declaration of Helsinki, Belmont report, and U.S. Common rule. In keeping with 45 CFR 46.104(d) [\n                      \n                      ], this study was performed utilizing retrospective, deidentified clinical data, and is considered IRB exempt with waivers of patient informed consent.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}]}}