{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:25:53Z","timestamp":1778221553250,"version":"3.51.4"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>We investigated the biological predisposition to site of metastasis in patients with NSCLC based on their molecular profiling and program death ligand PD-L1 status. We sought to identify any association between metastatic site and molecular profile in NSCLC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a retrospective analysis of patients with stage IV NSCLC who were newly diagnosed from January 2014 to June 2022. Clinical characteristics, pathology, molecular reports, and imaging were retrieved and analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 143 patients were included in the study. Median age was 65 years, with an equal number of men (n=71) and women (n=72). The most common histology was adenocarcinoma (81.8%). At least one genetic mutation was discovered in 100 patients. Mutations with a targetable drug were found in 86 patients. The most common mutations were <jats:italic>TP53<\/jats:italic> (25.2%), <jats:italic>EGFR<\/jats:italic> (24.5%), <jats:italic>KRAS\/NRAS<\/jats:italic> (20.3%), and <jats:italic>CDKN2A\/2B<\/jats:italic> (7.7%). Patients with any mutation were significantly more likely to have metastatic disease to the brain (57% <jats:italic>vs<\/jats:italic>. 37%, p=0.03), but there was no difference in metastatic disease to bone (34% <jats:italic>vs<\/jats:italic>. 26%, p=0.32). Patients without a discoverable mutation were significantly more likely to have metastatic disease to other sites (e.g., adrenal gland 91% <jats:italic>vs<\/jats:italic>. liver 66%, p=0.002). There was no difference in progression-free survival (PFS) or overall survival (OS) between those with versus without mutations. Median PFS and OS were significantly longer in patients with an <jats:italic>EGFR<\/jats:italic> mutation than those with <jats:italic>KRAS\/NRAS<\/jats:italic> or <jats:italic>TP53<\/jats:italic> mutations. Patients with PD-L1 &amp;gt;1% or <jats:italic>TP53<\/jats:italic> were significantly more likely to have metastatic disease to organs other than bone or brain (p=0.047 and p=0.023, respectively). We identified four prognostic groups in metastatic NSCLC. Patients with PD-L1 &amp;lt;1% and no actionable mutations have the poorest prognosis, with median survival of around 20 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with mutations discoverable on NGS are more likely to have metastatic disease to the brain. <jats:italic>KRAS\/NRAS<\/jats:italic> in particular has a predilection to metastasize to the brain and bone. PD-L1 expression and a <jats:italic>TP53<\/jats:italic> mutation, on the other hand, tend to lead to metastasis of NSCLC to organs other than brain or bone. These results need to be corroborated in larger prospective studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1212788","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T05:27:01Z","timestamp":1694582821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Genomic profiling and sites of metastasis in non-small cell lung cancer"],"prefix":"10.3389","volume":"13","author":[{"given":"Kok Hoe","family":"Chan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthi","family":"Sridhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Zheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Hassan 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