{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:40:51Z","timestamp":1786390851592,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Advanced non\u2010small cell lung cancer (NSCLC), particularly lung adenocarcinoma, remains a leading cause of cancer\u2010related mortality. Although molecular profiling has improved disease stratification, most biomarker assays rely on invasive tissue sampling. Exhaled breath condensate (EBC) is an attractive non\u2010invasive biofluid that may provide clinically relevant molecular information. This study evaluated whether cell\u2010free RNA (cfRNA) obtained from EBC can capture diagnostically and prognostically informative gene\u2010expression changes in advanced lung adenocarcinoma.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this prospective study, 40 patients with histologically confirmed stage IIIB\u2013IV lung adenocarcinoma and 20 healthy controls were enrolled. EBC samples were collected from all participants, and plasma samples were obtained from a subgroup of 10 patients and 10 controls. Expression of\n EGFR, FGFR2, PIK3CA, PTEN, SMAD4, STK11,<\/jats:italic>\n and\n TP53<\/jats:italic>\n was quantified by RT\u2010qPCR and normalized to GAPDH using the 2\n \u2212\u0394\u0394CT<\/jats:sup>\n method. Receiver operating characteristic (ROC) analysis, correlation testing, and Kaplan\u2013Meier survival analysis were performed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The most clinically relevant findings were observed for\n PIK3CA<\/jats:italic>\n ,\n FGFR2<\/jats:italic>\n , and\n EGFR<\/jats:italic>\n . In EBC,\n PIK3CA<\/jats:italic>\n emerged as the only gene with significant diagnostic performance for distinguishing patients from healthy controls (AUC\u2009=\u20090.8522; sensitivity 81.58%; specificity 76.92%). In survival analyses, high\n FGFR2<\/jats:italic>\n and high\n PIK3CA<\/jats:italic>\n expression were associated with significantly shorter overall survival, supporting their prognostic relevance. In treatment\u2010stratified analysis, low\n EGFR<\/jats:italic>\n expression was associated with longer survival in patients receiving chemotherapy alone, suggesting potential predictive value in this subgroup. In plasma,\n PIK3CA<\/jats:italic>\n was upregulated approximately five\u2010fold, whereas\n EGFR<\/jats:italic>\n was downregulated approximately five\u2010fold. Notably,\n EGFR<\/jats:italic>\n expression showed a strong positive correlation between EBC and plasma (\n R<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090.7849,\n p<\/jats:italic>\n \u2009=\u20090.0006), indicating cross\u2010matrix consistency for this marker. By contrast, alterations in\n PTEN<\/jats:italic>\n ,\n TP53<\/jats:italic>\n , and\n SMAD4<\/jats:italic>\n should be considered exploratory, as they showed differential expression but lacked comparable diagnostic, prognostic, or treatment\u2010associated strength.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n EBC\u2010based cfRNA profiling provides a feasible, non\u2010invasive approach for molecular characterization of advanced lung adenocarcinoma. Among the genes examined,\n PIK3CA<\/jats:italic>\n showed the strongest diagnostic signal,\n FGFR2<\/jats:italic>\n demonstrated prognostic significance, and\n EGFR<\/jats:italic>\n showed the clearest cross\u2010sample concordance and treatment\u2010associated relevance. Larger independent validation studies are required before clinical implementation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cnr2.70566","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:40:16Z","timestamp":1780486816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene Expression Profiling of\n EGFR<\/i>\n ,\n FGFR2<\/i>\n ,\n PIK3CA<\/i>\n ,\n PTEN<\/i>\n ,\n SMAD4<\/i>\n ,\n STK11<\/i>\n , and\n TP53<\/i>\n in Cell\u2010Free\n RNA<\/scp>\n From Exhaled Breath Condensate: Diagnostic, Prognostic, and Therapeutic Implications in Advanced Lung Adenocarcinoma"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7335-6322","authenticated-orcid":false,"given":"Sabina","family":"Latifova","sequence":"first","affiliation":[{"name":"Department of Basic Oncology, Faculty of Medicine Ege University Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2320-1940","authenticated-orcid":false,"given":"Uygar","family":"Genis","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Ege University Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-9172","authenticated-orcid":false,"given":"Haydar Soydaner","family":"Karakus","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Faculty of Medicine Ege University Izmir T\u00fcrkiye"},{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9317-2642","authenticated-orcid":false,"given":"Korcan","family":"Korba","sequence":"additional","affiliation":[{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir T\u00fcrkiye"},{"name":"Department of Chemical Technologies, Faculty of Engineering Ege University Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8993-674X","authenticated-orcid":false,"given":"Su","family":"Ozgur","sequence":"additional","affiliation":[{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir T\u00fcrkiye"},{"name":"WHO\/IARC\u2010GICR, Regional Cancer Registry in North Africa, Central and Western Asia Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3130-4739","authenticated-orcid":false,"given":"Ceyda","family":"Aldag","sequence":"additional","affiliation":[{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6089-1840","authenticated-orcid":false,"given":"Tuncay","family":"Goksel","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Faculty of Medicine Ege University Izmir T\u00fcrkiye"},{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8090-703X","authenticated-orcid":false,"given":"Levent","family":"Pelit","sequence":"additional","affiliation":[{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir T\u00fcrkiye"},{"name":"Department of Chemistry, Faculty of Science Ege Universit Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-3237","authenticated-orcid":false,"given":"Cumhur","family":"Gunduz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Ege University Izmir T\u00fcrkiye"},{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9890-3256","authenticated-orcid":false,"given":"Asli Tetik","family":"Vardarli","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Ege University Izmir T\u00fcrkiye"},{"name":"Translational Pulmonary Research Center (EgeSAM) Ege University Izmir 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