{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:46:21Z","timestamp":1782819981061,"version":"3.54.5"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>WD-repeat domain 1 (WDR1), a key regulator of actin cytoskeleton dynamics, has been implicated in tumor progression. However, its pan-cancer characteristics and immunological relevance remain unclear. In this study, we performed an integrative pan-cancer analysis to evaluate the expression patterns, prognostic value, molecular features, and immune associations of WDR1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically analyzed WDR1 across cancers using integrated datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO). By integrating R software and online bioinformatics platforms (e.g., UALCAN, HPA, GEPIA2, cBioPortal, and TIMER2.0), we characterized WDR1 in terms of expression, prognostic and diagnostic value, epigenetic regulation, genetic variation, and immune cell infiltration. Functional enrichment and drug sensitivity analyses were further conducted, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments were performed for validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WDR1 exhibited heterogeneous expression across cancers and showed tumor-type\u2013dependent prognostic significance. In addition, WDR1 displayed differential DNA methylation patterns and was positively correlated with multiple RNA methylation\u2013related regulators. Notably, WDR1 expression was closely associated with tumor immune microenvironment features, including increased infiltration of myeloid and stromal cells and broad correlations with immune checkpoint molecules and immune-related genes. Functional analyses indicated that WDR1-related genes were primarily involved in actin cytoskeleton organization. Drug sensitivity analysis revealed that WDR1 expression was associated with differential responses to multiple therapeutic agents. Importantly, experimental validation demonstrated that WDR1 exerted context-dependent biological effects, suppressing proliferation, migration, and invasion in renal cancer cells while promoting these phenotypes in gastric cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrated that WDR1 was associated with tumor progression and immune microenvironment remodeling in a context-dependent manner and may represent a potential biomarker for further investigation in cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1864405","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:01:37Z","timestamp":1782817297000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic pan-cancer analysis reveals context-dependent prognostic and immunological roles of WDR1 with divergent effects in renal and gastric cancers"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiu-shuang","family":"Li","sequence":"first","affiliation":[{"name":"College of Life and Health Sciences, Wuhan University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-xin","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences, Wuhan University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-yi","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences, Wuhan University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-chao","family":"Shi","sequence":"additional","affiliation":[{"name":"Central China Subcenter of National Center for Cardiovascular Diseases, Henan Cardiovascular Disease Center, Fuwai Central-China Cardiovascular Hospital, Central China Fuwai Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-yun","family":"Ru","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences, Wuhan University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-hui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences, Wuhan University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-zhu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences, Wuhan University of Science and Technology","place":["Wuhan, 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