{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:30:15Z","timestamp":1792045815107,"version":"4.4.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["1I01BX004872-01"],"award-info":[{"award-number":["1I01BX004872-01"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Lung cancer is the leading cause of cancer-related deaths, of which adenocarcinoma is the most common subtype. Despite this, lung adenocarcinoma and its metastasis are poorly understood, due to difficulties in feasibly recapitulating disease progression and predicting clinical benefits of therapy. We outline a methodology to develop immunogenic orthotopic lung adenocarcinoma mouse models, by injecting cell-specific cre viruses into the lung of a genetically engineered mouse, which mirrors cancer progression defined by the International Association for the Study of Lung Cancer. Evaluation of different cre virus\/concentrations models demonstrate remarkable consistency in cancer initiation and metastasis, allowing for high throughput, while showing differences in timing and severity, offering greater flexibility when selecting models. Histological and immune profiles reflect clinical observations suggesting similar mechanisms are recapitulated and preliminary data show resultant tumors to be responsive to clinical treatments. We present a clinically relevant, next-generation murine model for studying lung adenocarcinoma.<\/jats:p>","DOI":"10.1038\/s41598-025-90344-1","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T06:04:52Z","timestamp":1740722692000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Methodology of murine lung cancer mimics clinical lung adenocarcinoma progression and metastasis"],"prefix":"10.1038","volume":"15","author":[{"given":"Edison Q.","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Y.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Knott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Bang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose R.","family":"Conejo-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhi","family":"Wangpaichitr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane C.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"90344_CR1","doi-asserted-by":"crossref","unstructured":"Tsao, M-S., Nicholson, A. G., Maleszewski, J. J., Marx, A. & Travis, W. D. Reprint of Introduction to 2021 WHO Classification of Thoracic Tumors 337\u2013340 (Elsevier, 2022).","DOI":"10.1016\/j.jtho.2022.01.008"},{"key":"90344_CR2","doi-asserted-by":"crossref","unstructured":"Rami-Porta, R., Goldstraw, P. & Pass, H. I. The Eighth Edition of the Tumor, node, and Metastasis Classification of lung cancer 253\u2212\u200964.e1 (Elsevier, 2018).","DOI":"10.1016\/B978-0-323-52357-8.00025-1"},{"issue":"6","key":"90344_CR3","doi-asserted-by":"publisher","first-page":"545","DOI":"10.3390\/metabo12060545","volume":"12","author":"H Mari\u00ebn","year":"2022","unstructured":"Mari\u00ebn, H. et al. Changes in metabolism as a diagnostic tool for lung cancer: Systematic review. Metabolites 12 (6), 545 (2022).","journal-title":"Metabolites"},{"issue":"9","key":"90344_CR4","doi-asserted-by":"publisher","first-page":"170070","DOI":"10.1098\/rsob.170070","volume":"7","author":"S Blandin Knight","year":"2017","unstructured":"Blandin Knight, S. et al. Progress and prospects of early detection in lung cancer. Open. Biol. 7 (9), 170070 (2017).","journal-title":"Open. Biol."},{"issue":"2","key":"90344_CR5","doi-asserted-by":"publisher","first-page":"762","DOI":"10.21037\/tcr-23-1816","volume":"13","author":"S Alamri","year":"2024","unstructured":"Alamri, S. et al. Disease prognosis and therapeutic strategies in patients with advanced non-small cell lung cancer (NSCLC): A 6-year epidemiological study between 2015\u20132021. Transl. Cancer Res. 13 (2), 762 (2024).","journal-title":"Transl. Cancer Res."},{"issue":"5","key":"90344_CR6","doi-asserted-by":"publisher","first-page":"e314S","DOI":"10.1378\/chest.12-2360","volume":"143","author":"N Ramnath","year":"2013","unstructured":"Ramnath, N. et al. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer\u2014American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143 (5), e314S\u2013e40S (2013).","journal-title":"Chest"},{"issue":"8","key":"90344_CR7","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1097\/JTO.0b013e31812f3c1a","volume":"2","author":"P Goldstraw","year":"2007","unstructured":"Goldstraw, P. et al. The IASLC lung cancer staging project: Proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J. Thorac. Oncol. 2 (8), 706\u2013714 (2007).","journal-title":"J. Thorac. Oncol."},{"key":"90344_CR8","doi-asserted-by":"crossref","unstructured":"Rami-Porta, R. et al. The international association for the study of lung cancer lung cancer staging project: Proposals for revision of the TNM stage groups in the forthcoming (Ninth) edition of the TNM classification for lung cancer. J. Thorac. Oncol. (2024).","DOI":"10.1016\/j.jtho.2024.02.011"},{"issue":"1","key":"90344_CR9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","volume":"70","author":"RL Siegel","year":"2020","unstructured":"Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 70 (1), 7\u201330 (2020).","journal-title":"CA Cancer J. Clin."},{"issue":"1","key":"90344_CR10","first-page":"103","volume":"55","author":"HC Kim","year":"2022","unstructured":"Kim, H. C. et al. Five-year overall survival and prognostic factors in patients with lung cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015. Cancer Res. Treatment: Official J. Korean Cancer Association. 55 (1), 103\u2013111 (2022).","journal-title":"Cancer Res. Treatment: Official J. Korean Cancer Association"},{"issue":"12","key":"90344_CR11","doi-asserted-by":"publisher","first-page":"5574","DOI":"10.1002\/cam4.2474","volume":"8","author":"H Dillekas","year":"2019","unstructured":"Dillekas, H., Rogers, M. S. & Straume, O. Are 90% of deaths from cancer caused by metastases? Cancer Med. 8 (12), 5574\u20135576 (2019).","journal-title":"Cancer Med."},{"issue":"1","key":"90344_CR12","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ccm.2019.11.001","volume":"41","author":"WD Travis","year":"2020","unstructured":"Travis, W. D. Lung cancer pathology: Current concepts. Clin. Chest Med. 41 (1), 67\u201385 (2020).","journal-title":"Clin. Chest Med."},{"key":"90344_CR13","doi-asserted-by":"crossref","unstructured":"Potter, A. L. et al. Association of computed tomography screening with lung cancer stage shift and survival in the United States: Quasi-experimental study. Bmj 376, e069008 (2022).","DOI":"10.1136\/bmj-2021-069008"},{"issue":"1","key":"90344_CR14","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1186\/s12885-023-11074-z","volume":"23","author":"H Bailey","year":"2023","unstructured":"Bailey, H. et al. Treatment patterns and outcomes of patients with metastatic non-small cell lung cancer in five European countries: a real-world evidence survey. BMC Cancer 23 (1), 603 (2023).","journal-title":"BMC Cancer"},{"key":"90344_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12885-020-06734-3","volume":"20","author":"RN Hansen","year":"2020","unstructured":"Hansen, R. N. et al. Long-term survival trends in patients with unresectable stage III non-small cell lung cancer receiving chemotherapy and radiation therapy: A SEER cancer registry analysis. BMC Cancer 20, 1\u20136 (2020).","journal-title":"BMC cancer"},{"issue":"6","key":"90344_CR16","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.3390\/jcm11061738","volume":"11","author":"A Agbarya","year":"2022","unstructured":"Agbarya, A. et al. Real-world journey of unresectable stage III NSCLC patients: Current dilemmas for disease staging and treatment. J. Clin. Med. 11 (6), 1738 (2022).","journal-title":"J. Clin. Med."},{"issue":"1","key":"90344_CR17","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 72 (1), 7\u201333 (2022).","journal-title":"CA Cancer J. Clin."},{"key":"90344_CR18","doi-asserted-by":"publisher","first-page":"621324","DOI":"10.1155\/2015\/621324","volume":"2015","author":"A Kellar","year":"2015","unstructured":"Kellar, A., Egan, C. & Morris, D. Preclinical murine models for lung cancer: Clinical trial applications. Biomed. Res. Int. 2015, 621324 (2015).","journal-title":"Biomed. Res. Int."},{"issue":"5","key":"90344_CR19","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1152\/jappl.2000.88.5.1551","volume":"88","author":"WA Altemeier","year":"2000","unstructured":"Altemeier, W. A., McKinney, S. & Glenny, R. W. Fractal nature of regional ventilation distribution. J. Appl. Physiol. 88 (5), 1551\u20131557 (2000).","journal-title":"J. Appl. Physiol."},{"issue":"22","key":"90344_CR20","doi-asserted-by":"publisher","first-page":"10280","DOI":"10.1158\/0008-5472.CAN-05-2193","volume":"65","author":"EL Jackson","year":"2005","unstructured":"Jackson, E. L. et al. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res. 65 (22), 10280\u201310288 (2005).","journal-title":"Cancer Res."},{"key":"90344_CR21","doi-asserted-by":"crossref","unstructured":"Safari, R. & Meuwissen, R. Practical use of advanced mouse models for lung cancer. Mouse Models Cancer: Methods Protocols 1267, 93\u2013124 (2015).","DOI":"10.1007\/978-1-4939-2297-0_5"},{"issue":"6","key":"90344_CR22","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.cell.2004.11.004","volume":"119","author":"KP Olive","year":"2004","unstructured":"Olive, K. P. et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 119 (6), 847\u2013860 (2004).","journal-title":"Cell"},{"issue":"7345","key":"90344_CR23","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nature09881","volume":"473","author":"MM Winslow","year":"2011","unstructured":"Winslow, M. M. et al. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473 (7345), 101\u2013104 (2011).","journal-title":"Nature"},{"issue":"24","key":"90344_CR24","doi-asserted-by":"publisher","first-page":"3243","DOI":"10.1101\/gad.943001","volume":"15","author":"EL Jackson","year":"2001","unstructured":"Jackson, E. L. et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15 (24), 3243\u20133248 (2001).","journal-title":"Genes Dev."},{"issue":"7","key":"90344_CR25","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1038\/nprot.2009.95","volume":"4","author":"M DuPage","year":"2009","unstructured":"DuPage, M., Dooley, A. L. & Jacks, T. Conditional mouse lung cancer models using adenoviral or lentiviral delivery of cre recombinase. Nat. Protoc. 4 (7), 1064\u20131072 (2009).","journal-title":"Nat. Protoc."},{"issue":"10","key":"90344_CR26","doi-asserted-by":"publisher","first-page":"e267","DOI":"10.1038\/oncsis.2016.65","volume":"5","author":"MR Sheen","year":"2016","unstructured":"Sheen, M. R. et al. Constitutively activated PI3K accelerates tumor initiation and modifies histopathology of breast cancer. Oncogenesis 5 (10), e267\u2013e (2016).","journal-title":"Oncogenesis"},{"issue":"4","key":"90344_CR27","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.ccell.2016.09.001","volume":"30","author":"G Ferone","year":"2016","unstructured":"Ferone, G. et al. SOX2 is the determining oncogenic switch in promoting lung squamous cell carcinoma from different cells of origin. Cancer Cell. 30 (4), 519\u2013532 (2016).","journal-title":"Cancer Cell."},{"issue":"9","key":"90344_CR28","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.21037\/tlcr-23-331","volume":"12","author":"H Iso","year":"2023","unstructured":"Iso, H. et al. Thyroid transcription factor-1 (TTF-1) expression and the efficacy of combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapy in non-squamous non-small cell lung cancer. Transl. Lung Cancer Res. 12 (9), 1850 (2023).","journal-title":"Transl. Lung Cancer Res."},{"issue":"2","key":"90344_CR29","doi-asserted-by":"publisher","first-page":"163","DOI":"10.5858\/arpa.2011-0320-OA","volume":"136","author":"BM Turner","year":"2012","unstructured":"Turner, B. M. et al. A new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by tissue microarray. Arch. Pathol. Lab. Med. 136 (2), 163\u2013171 (2012).","journal-title":"Arch. Pathol. Lab. Med."},{"issue":"1","key":"90344_CR30","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1101\/gad.10.1.60","volume":"10","author":"S Kimura","year":"1996","unstructured":"Kimura, S. et al. The T\/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev. 10 (1), 60\u201369 (1996).","journal-title":"Genes Dev."},{"issue":"9","key":"90344_CR31","first-page":"5671","volume":"14","author":"RJ Bohinski","year":"1994","unstructured":"Bohinski, R. J., Di Lauro, R. & Whitsett, J. A. The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis. Mol. Cell. Biol. 14 (9), 5671\u20135681 (1994).","journal-title":"Mol. Cell. Biol."},{"issue":"5","key":"90344_CR32","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1309\/AJCPKVBXTI9O3TEM","volume":"138","author":"S Mukhopadhyay","year":"2012","unstructured":"Mukhopadhyay, S. & Katzenstein, A-L-A. Comparison of monoclonal napsin A, polyclonal napsin A, and TTF-1 for determining lung origin in metastatic adenocarcinomas. Am. J. Clin. Pathol. 138 (5), 703\u2013711 (2012).","journal-title":"Am. J. Clin. Pathol."},{"issue":"10","key":"90344_CR33","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1038\/modpathol.3800422","volume":"18","author":"E Comp\u00e9rat","year":"2005","unstructured":"Comp\u00e9rat, E. et al. Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin. Mod. Pathol. 18 (10), 1371\u20131376 (2005).","journal-title":"Mod. Pathol."},{"key":"90344_CR34","doi-asserted-by":"publisher","first-page":"613099","DOI":"10.3389\/pore.2021.613099","volume":"27","author":"S Weidemann","year":"2021","unstructured":"Weidemann, S. et al. Napsin A expression in human tumors and normal tissues. Pathol. Oncol. Res. 27, 613099 (2021).","journal-title":"Pathol. Oncol. Res."},{"issue":"3","key":"90344_CR35","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1097\/PAS.0b013e31823b13e2","volume":"36","author":"NG Ordonez","year":"2012","unstructured":"Ordonez, N. G. A word of caution regarding napsin A expression in squamous cell carcinomas of the lung. Am. J. Surg. Pathol. 36 (3), 396\u2013401 (2012).","journal-title":"Am. J. Surg. Pathol."},{"issue":"4","key":"90344_CR36","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1097\/PAI.0b013e318205b059","volume":"19","author":"J Ye","year":"2011","unstructured":"Ye, J. et al. Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung. Appl. Immunohistochem. Mol. Morphology. 19 (4), 313\u2013317 (2011).","journal-title":"Appl. Immunohistochem. Mol. Morphology"},{"key":"90344_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12885-016-2169-5","volume":"16","author":"F-Y Niu","year":"2016","unstructured":"Niu, F-Y. et al. Distribution and prognosis of uncommon metastases from non-small cell lung cancer. BMC Cancer 16, 1\u20136 (2016).","journal-title":"BMC Cancer"},{"issue":"7","key":"90344_CR38","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1038\/sj.bjc.6690178","volume":"79","author":"Y Doki","year":"1999","unstructured":"Doki, Y. et al. Mediastinal lymph node metastasis model by orthotopic intrapulmonary implantation of Lewis lung carcinoma cells in mice. Br. J. Cancer 79 (7), 1121\u20131126 (1999).","journal-title":"Br. J. Cancer"},{"issue":"26","key":"90344_CR39","doi-asserted-by":"publisher","first-page":"43427","DOI":"10.18632\/oncotarget.15238","volume":"8","author":"C Liu","year":"2017","unstructured":"Liu, C. et al. Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy. Oncotarget 8 (26), 43427 (2017).","journal-title":"Oncotarget"},{"key":"90344_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12943-016-0551-1","volume":"15","author":"EA Marshall","year":"2016","unstructured":"Marshall, E. A. et al. Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis. Mol. Cancer 15, 1\u201315 (2016).","journal-title":"Mol. Cancer"},{"issue":"1","key":"90344_CR41","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13045-020-0843-1","volume":"13","author":"Z Yang","year":"2020","unstructured":"Yang, Z. et al. Myeloid-derived suppressor cells: New and exciting players in lung cancer. J. Hematol. Oncol. 13 (1), 10 (2020).","journal-title":"J. Hematol. Oncol."},{"issue":"8","key":"90344_CR42","doi-asserted-by":"publisher","first-page":"e14317","DOI":"10.1111\/ijcp.14317","volume":"75","author":"X Tian","year":"2021","unstructured":"Tian, X. et al. Circulating CD15\u2009+\u2009LOX-1\u2009+\u2009PMN\u2010MDSCs are a potential biomarker for the early diagnosis of non\u2010small\u2010cell lung cancer. Int. J. Clin. Pract. 75 (8), e14317 (2021).","journal-title":"Int. J. Clin. Pract."},{"issue":"42","key":"90344_CR43","doi-asserted-by":"publisher","first-page":"e31307","DOI":"10.1097\/MD.0000000000031307","volume":"101","author":"T Chen","year":"2022","unstructured":"Chen, T., Chen, H., Lu, W. & Yao, Y. T lymphocyte subsets and PD-1 expression on lymphocytes in peripheral blood of patients with non-small cell lung cancer. Medicine 101 (42), e31307 (2022).","journal-title":"Medicine"},{"key":"90344_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12865-018-0241-4","volume":"19","author":"J Jackute","year":"2018","unstructured":"Jackute, J. et al. Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer. BMC Immunol. 19, 1\u201313 (2018).","journal-title":"BMC Immunol."},{"key":"90344_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2407-10-112","volume":"10","author":"J Ma","year":"2010","unstructured":"Ma, J. et al. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC cancer. 10, 1\u20139 (2010).","journal-title":"BMC cancer"},{"issue":"1","key":"90344_CR46","doi-asserted-by":"publisher","first-page":"1935557","DOI":"10.1080\/2162402X.2021.1935557","volume":"10","author":"GF Van Wigcheren","year":"2021","unstructured":"Van Wigcheren, G. F. et al. Cisplatin inhibits frequency and suppressive activity of monocytic myeloid-derived suppressor cells in cancer patients. Oncoimmunology 10 (1), 1935557 (2021).","journal-title":"Oncoimmunology"},{"key":"90344_CR47","doi-asserted-by":"crossref","unstructured":"Cao, L. et al. M2 macrophage infiltration into tumor islets leads to poor prognosis in non-small-cell lung cancer. Cancer Manage. Res. 11, 6125\u20136138 (2019).","DOI":"10.2147\/CMAR.S199832"},{"issue":"16","key":"90344_CR48","doi-asserted-by":"publisher","first-page":"5247","DOI":"10.1158\/1078-0432.CCR-10-2805","volume":"17","author":"K Suzuki","year":"2011","unstructured":"Suzuki, K. et al. Prognostic immune markers in non-small cell lung cancer. Clin. Cancer Res. 17 (16), 5247\u20135256 (2011).","journal-title":"Clin. Cancer Res."},{"issue":"1","key":"90344_CR49","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","volume":"141","author":"B-Z Qian","year":"2010","unstructured":"Qian, B-Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141 (1), 39\u201351 (2010).","journal-title":"Cell"},{"issue":"1","key":"90344_CR50","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13045-023-01436-2","volume":"16","author":"SM Liu","year":"2023","unstructured":"Liu, S. M. et al. Emerging evidence and treatment paradigm of non-small cell lung cancer. J. Hematol. Oncol. 16 (1), 40 (2023).","journal-title":"J. Hematol. Oncol."},{"issue":"12","key":"90344_CR51","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1001\/jamaoncol.2021.4932","volume":"7","author":"AK Ganti","year":"2021","unstructured":"Ganti, A. K., Klein, A. B., Cotarla, I., Seal, B. & Chou, E. Update of incidence, prevalence, survival, and initial treatment in patients with non-small cell lung cancer in the US. JAMA Oncol. 7 (12), 1824\u20131832 (2021).","journal-title":"JAMA Oncol."},{"issue":"11","key":"90344_CR52","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.7150\/jca.40196","volume":"11","author":"T Tsiouda","year":"2020","unstructured":"Tsiouda, T. et al. Sex differences and adverse effects between chemotherapy and immunotherapy for non-small cell lung cancer. J. Cancer 11 (11), 3407 (2020).","journal-title":"J. Cancer"},{"issue":"6","key":"90344_CR53","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s00408-023-00661-3","volume":"201","author":"AEC Daylan","year":"2023","unstructured":"Daylan, A. E. C., Miao, E., Tang, K., Chiu, G. & Cheng, H. Lung Cancer in Never smokers: delving into Epidemiology, genomic and Immune Landscape, Prognosis, Treatment, and screening. Lung 201 (6), 521\u2013529 (2023).","journal-title":"Lung"},{"key":"90344_CR54","doi-asserted-by":"crossref","unstructured":"Sheen, M. R., Warner, S. L., Fields, J. L., Conejo-Garcia, J. R. & Fiering, S. Myristoylated p110\u03b1 causes embryonic death due to developmental and vascular defects. Open. Life Sci.  10(1), 461-478 (2015).","DOI":"10.1515\/biol-2015-0048"},{"issue":"3","key":"90344_CR55","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.neuroimage.2006.01.015","volume":"31","author":"PA Yushkevich","year":"2006","unstructured":"Yushkevich, P. A. et al. User-guided 3D active contour segmentation of anatomical structures: Significantly improved efficiency and reliability. Neuroimage 31 (3), 1116\u20131128 (2006).","journal-title":"Neuroimage"},{"issue":"2","key":"90344_CR56","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1679\/aohc.66.123","volume":"66","author":"T Kawamoto","year":"2003","unstructured":"Kawamoto, T. Use of a new adhesive film for the preparation of multi-purpose fresh-frozen sections from hard tissues, whole-animals, insects and plants. Arch. Histol. Cytol. 66 (2), 123\u2013143 (2003).","journal-title":"Arch. Histol. Cytol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90344-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90344-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90344-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T06:34:22Z","timestamp":1740724462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-90344-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["90344"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-90344-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,28]]},"assertion":[{"value":"19 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7127"}}