{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:07:17Z","timestamp":1783548437629,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2020MH249"],"award-info":[{"award-number":["ZR2020MH249"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite recent improvements in treatment technologies, such as surgical resection and chemoradiotherapy, the prognosis of patients with esophagogastric junction adenocarcinoma (EJA) remains poor due to early lymph node metastasis. Since few studies have investigated genes associated with lymph node metastasis in EJA, we aimed to screen lymph node metastasis\u2010associated genes and clarify their expression status and prognostic significance in EJA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The differential frequency of mutations between carcinoma and para\u2010carcinoma tissues from 199 cases with EJA was detected using targeted next\u2010generation sequencing (tNGS). Following a stratified analysis to determine that gender has no effect on the frequency of gene mutations, lymph node metastasis\u2010related genes, including <jats:italic>CDK6<\/jats:italic>, <jats:italic>MET<\/jats:italic>, <jats:italic>NOTCH1<\/jats:italic>, and <jats:italic>LRP1B<\/jats:italic>, were screened, and <jats:italic>CDK6<\/jats:italic> and <jats:italic>LRP1B<\/jats:italic> were selected for further study as they displayed significant differences in mutation rates. Differences in their expression status were verified using immunohistochemical (IHC) staining in 18 <jats:italic>CDK6<\/jats:italic>\u2010 and 17 <jats:italic>LRP1B<\/jats:italic>\u2010mutated samples and a randomly matched control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>tNGS revealed that <jats:italic>CDK6<\/jats:italic> and <jats:italic>LRP1B<\/jats:italic> mutation frequencies were significantly different between EJA cases with (<jats:italic>N<\/jats:italic>\u00a0\u2265\u00a01) or without (<jats:italic>N<\/jats:italic>\u00a0=\u00a00) lymph node metastasis. In particular, <jats:italic>CDK6<\/jats:italic> mutation frequency was expected less, whereas that of <jats:italic>LRP1B<\/jats:italic> was remarkably higher in cases with stage N0 than in those with stage <jats:italic>N<\/jats:italic>\u00a0\u2265\u00a01. IHC staining confirmed significant differences in <jats:italic>CDK6<\/jats:italic> and <jats:italic>LRP1B<\/jats:italic> expression status between the study and control cohorts. Chi\u2010square tests revealed that a high <jats:italic>CDK6<\/jats:italic> expression status correlated significantly with smoking history (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.044), T stage (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.035), N stage (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.000), and advanced TNM stage (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.001) in EJA, whereas a high <jats:italic>LRP1B<\/jats:italic> expression status only correlated with BMI (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.013) and N stage (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.000). Furthermore, as confirmed by survival status investigation, a high <jats:italic>LRP1B<\/jats:italic> expression status predicted good prognosis, and a high <jats:italic>CDK6<\/jats:italic> expression status was an independent predictor of poor prognosis in patients with EJA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, the findings of this study demonstrate that a high <jats:italic>CDK6<\/jats:italic> and <jats:italic>LRP1B<\/jats:italic> expression status promotes and inhibits lymph node metastasis in patients with EJA, respectively, suggesting that both <jats:italic>CDK6<\/jats:italic> and <jats:italic>LRP1B<\/jats:italic> are significantly potential predictors of lymph node metastasis and prognosis in EJA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4065","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T09:46:08Z","timestamp":1624268768000},"page":"5088-5100","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Screening and clinical significance of lymph node metastasis\u2010related genes within esophagogastric junction adenocarcinoma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2281-7129","authenticated-orcid":false,"given":"Rui","family":"Han","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Province P. 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