{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:02:39Z","timestamp":1780470159577,"version":"3.54.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Uterine corpus endometrial carcinoma (UCEC) incidence rises globally, with &amp;gt;50% of advanced\/recurrent patients showing poor response to immune checkpoint inhibitors due to inadequate biomarkers. Protein tyrosine kinase 6 (PTK6), aberrantly expressed in malignancies and linked to tumor progression, lacks defined clinical significance in UCEC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Multi-omics analysis utilized UCEC RNA-seq (TCGA\/GEO) and proteomics (CPTAC). PTK6 protein interactors from STRING were used for functional enrichment analysis. Tumor microenvironment (TME) was assessed via ESTIMATE (stromal\/immune scores), TIMER3 (immune infiltration), and TCIA (immunophenoscore, IPS). Immunohistochemistry (IHC) validation (\n                      <jats:italic>n<\/jats:italic>\n                      =\u202f200) explored the prognostic value.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PTK6 was upregulated in UCEC (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001) with promoter hypomethylation (median \u03b2: 0.32 vs. normal 0.52,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), highest in microsatellite instability-high (MSI-H) subtype, and correlated with tumor mutational burden (TMB). High PTK6 expression associated with worse overall survival (OS) in both entire cohort (HR\u202f=\u202f2.065, 95% CI 1.060\u20134.203,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.033) and MSI-H subtype (HR\u202f=\u202f8.562, 95% CI 2.226\u201332.930,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0018). Exploratory analysis suggested low PTK6-linked reduced progression-free survival in POLE subtype (HR\u202f=\u202f10.48, 95% CI 1.063\u2013103.4,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.044; wide CI suggests caution). PTK6-related genes were mainly involved in ERBB signaling, PD-1\/PD-L1 immune checkpoint in cancers, and focal adhesion. Upregulated PTK6 was associated with an altered TME (increased neutrophils, decreased CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, reduced IPS; all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). IHC confirmed PTK6 overexpression as an independent poor prognostic factor for OS (HR\u202f=\u202f5.050, 95% CI 2.136\u201311.943,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), associating with aggressive clinicopathological features (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PTK6 represents a context-dependent prognostic biomarker linked to tumor immune microenvironment remodeling in UCEC, suggesting its potential utility for immunotherapeutic optimization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1842564","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:06:33Z","timestamp":1780466793000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated PTK6 expression is associated with tumor immune microenvironment remodeling and predicts poor prognosis in endometrial carcinoma"],"prefix":"10.3389","volume":"13","author":[{"given":"Zebiao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology, Guangdong Engineering Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics (Proposed)\/GuangDong Engineering Technology Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]},{"name":"Laboratory of Human Virology and Oncology, Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiongyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Central Laboratory, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Guangdong Engineering Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics (Proposed)\/GuangDong Engineering Technology Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Second Affiliated Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaibing","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Human Virology and Oncology, Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haituo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Guangdong Engineering Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics (Proposed)\/GuangDong Engineering Technology Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Guangdong Engineering Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics (Proposed)\/GuangDong Engineering Technology Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Guangdong Engineering Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics (Proposed)\/GuangDong Engineering Technology Research Center of AI-Powered Precision Cancer Diagnostics and Therapeutics, Cancer Hospital of Shantou University Medical College","place":["Shantou, China"]},{"name":"Laboratory of Human Virology and Oncology, Shantou University Medical College","place":["Shantou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Guangdong Engineering Research 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