{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T16:49:08Z","timestamp":1775666948117,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"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. Genet."],"abstract":"<jats:p>In the present study, we aimed to investigate the clinical and prognostic values of<jats:italic>CDK4<\/jats:italic>amplification and improve the risk stratification in patients with esophageal squamous cell carcinoma.<jats:italic>CDK4<\/jats:italic>amplification was analyzed by fluorescence<jats:italic>in situ<\/jats:italic>hybridization using tissue microarray consisting of representative tissues of 520 patients with esophageal squamous cell carcinoma, and its correlation with clinicopathological features and clinical outcomes were evaluated.<jats:italic>CDK4<\/jats:italic>amplification was found in 8.5% (44\/520) of patients with esophageal squamous cell carcinoma.<jats:italic>CDK4<\/jats:italic>amplification was negatively correlated with disease progression (<jats:italic>P<\/jats:italic>= 0.003) and death (<jats:italic>P<\/jats:italic>= 0.006). Patients with<jats:italic>CDK4<\/jats:italic>amplification showed a significantly better disease-free survival (<jats:italic>P<\/jats:italic>= 0.016) and overall survival (<jats:italic>P<\/jats:italic>= 0.023) compared with those patients without<jats:italic>CDK4<\/jats:italic>amplification. When patients were further stratified into I\u2013II stage groups and III\u2013IV stage groups,<jats:italic>CDK4<\/jats:italic>amplification was significantly associated with both better disease-free survival (<jats:italic>P<\/jats:italic>= 0.023) and overall survival (<jats:italic>P<\/jats:italic>= 0.025) in the I\u2013II stage group rather than the III\u2013IV stage group. On univariate and multivariate analysis, invasive depth and<jats:italic>CDK4<\/jats:italic>amplification were associated with disease-free survival and overall survival. Taken together,<jats:italic>CDK4<\/jats:italic>amplification was identified as an independent prognostic factor for survival, which could be incorporated into the tumor\u2013node\u2013metastasis staging system to refine risk stratification of patients with esophageal squamous cell carcinoma.<\/jats:p>","DOI":"10.3389\/fgene.2021.616110","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T07:53:33Z","timestamp":1619682813000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["CDK4 Amplification in Esophageal Squamous Cell Carcinoma Associated With Better Patient Outcome"],"prefix":"10.3389","volume":"12","author":[{"given":"Jie","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Luan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Licheng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijie","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieakesu","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingyong","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/s0002-9440(10)65257-1","article-title":"Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation.","volume":"154","author":"An","year":"1999","journal-title":"Am. 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