{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:07:12Z","timestamp":1788955632302,"version":"build-2803163510"},"reference-count":92,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":251,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172991"],"award-info":[{"award-number":["82172991"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetics Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      To explore the prognostic value and immunomodulatory role of\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      in pancreatic ductal adenocarcinoma (PDAC), so as to provide evidence for the diagnosis and individualized treatment of PDAC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Next\u2010generation sequencing (NGS) was performed to detect 425 cancer\u2010associated genes in PDAC specimens and matched normal pancreatic tissues. Integrative transcriptome analysis based on TCGA, GTEx, and multiple GEO datasets was conducted to identify the differential expression of\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      between PDAC and normal pancreatic tissues. The Human Protein Atlas (HPA,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.proteinatlas.org\/\">https:\/\/www.proteinatlas.org\/<\/jats:ext-link>\n                      ) database was used to verify the protein expression and subcellular localization of\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      in normal pancreatic tissues and pancreatic ductal adenocarcinoma (PDAC) tissues. Single\u2010cell RNA\u2010sequencing and spatial transcriptomic data were further supplemented to delineate its cellular expression landscape. Forest plot, Kaplan\u2013Meier survival analysis, and ROC curve analysis were applied to evaluate the correlations between\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      expression and prognostic and to verify its prognostic accuracy. The prognostic reliability was further validated using the independent cohort GSE57495. Immune cell infiltration and immune regulatory factors were quantified via TIMER, EPIC, MCPcounter, CIBERSORT, and xCell algorithms, and TMEscore was calculated to predict the responsiveness to immune checkpoint blockade (ICB). Pharmacogenomic datasets including GDSC1, GDSC2, PRISM, and CTRP were utilized to screen optimal candidate drugs for\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      \u2010high PDAC patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      was significantly overexpressed in PDAC compared with normal pancreatic tissues. HPA immunohistochemistry confirmed\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      shifts from membranous to cytoplasmic localization in PDAC, indicating activated Wnt signaling and concordant dysregulation at mRNA and protein levels.\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      protein was mainly localized in malignant epithelial cells of PDAC, with elevated expression also observed in partial immune cell subsets by single\u2010cell sequencing and spatial transcriptome assessment. Upregulated\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      was significantly linked to unfavorable clinical prognosis in PDAC. ROC analysis verified its good diagnostic efficiency for distinguishing PDAC from peritumoral tissues with favorable sensitivity and specificity.\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      expression was closely correlated with multiple immune biomarker molecules and ICB therapeutic efficacy; patients with low\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      expression tended to be more responsive to ICB treatment. Pharmacological prediction revealed that PDAC patients with high\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      expression exhibited enhanced sensitivity to clofibrate and several other small\u2010molecule compounds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      may be remarkably effective as a suitable biomarker for the prognosis prediction of PDAC patients and is closely related to the tumor immune microenvironment. Such an association could provide novel thoughts for the therapy tactics and mechanistic studies toward PDAC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/genr\/8700258","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:22:06Z","timestamp":1788952926000},"source":"Crossref","is-referenced-by-count":0,"title":["Prognostic and Immunological Value of\n                    <i>CTNNB1<\/i>\n                    in Pancreatic Adenocarcinoma: A Comprehensive NGS and Multicomponent 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