{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T09:48:42Z","timestamp":1760521722051,"version":"3.41.2"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"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. Bioeng. Biotechnol."],"abstract":"<jats:p>Lymphatic metastasis influences clinical treatment and prognosis of patients with non-small-cell lung cancer (NSCLC). There is an urgency to understand the molecular features and mechanisms of lymph node metastasis. We analyzed the molecular features on pairs of the primary tumor and lymphatic metastasis tissue samples from 15 NSCLC patients using targeted next-generation sequencing. The potential metastasis-related genes were screened from our cohort based on cancer cell fraction. After filtering with gene functions, candidate metastasis-related events were validated in the MSK cohort with Fisher\u2019s exact test. The molecular signature and tumor mutational burden were similar in paired samples, and the average mutational concordance was 42.0% \u00b1 28.9%. Its metastatic mechanism is potentially a linear progression based on the metastatic seeding theory. Furthermore, mutated ataxia telangiectasia mutated and Rad3-related (<jats:italic>ATR<\/jats:italic>) and tet methylcytosine dioxygenase 2 (<jats:italic>TET2<\/jats:italic>) genes were significantly enriched in lymphatic metastases (<jats:italic>p<\/jats:italic> \u2264 0.05). Alterations in these two genes could be considered metastasis-related driving events. Mutated <jats:italic>ATR<\/jats:italic> and <jats:italic>TET2<\/jats:italic> might play an active role in the metastasis of lymph nodes with NSCLC. More case enrollment and long-term follow-up will further verify the clinical significance of these two genes.<\/jats:p>","DOI":"10.3389\/fbioe.2022.909388","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T12:52:16Z","timestamp":1658148736000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Features in Lymphatic Metastases Reflect the Metastasis Mechanism of Lymph Nodes With Non-Small-Cell Lung Cancers"],"prefix":"10.3389","volume":"10","author":[{"given":"Nannan","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongying","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyan","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruilin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhigong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongjiang","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaojun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of Mutational Processes in Human Cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13073-018-0539-0","article-title":"MutationalPatterns: Comprehensive Genome-wide Analysis of Mutational Processes","volume":"10","author":"Blokzijl","year":"2018","journal-title":"Genome Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1158\/2159-8290.CD-15-0369","article-title":"Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets","volume":"5","author":"Brastianos","year":"2015","journal-title":"Cancer Discov."},{"key":"B4","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/1759-7714.12970","article-title":"Lymph Node Metastasis in Chinese Patients with Clinical T1 Non-small Cell Lung Cancer: A Multicenter Real-World Observational Study","volume":"10","author":"Chen","year":"2019","journal-title":"Thorac. 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