{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:08:50Z","timestamp":1774980530320,"version":"3.50.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ21H080001"],"award-info":[{"award-number":["LQ21H080001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The distinct roles of GSK3 isoforms (GSK3\u03b1\/\u03b2) in tumorigenesis and immune modulation remain poorly characterized across malignancies. We integrated multi-omics data from TCGA, GTEx, and single-cell RNA-seq to analyze GSK3\u03b1\/\u03b2 expression patterns in 31 cancers. Functional clustering, survival analysis (Cox regression), immune infiltration, and in vitro validation (AML cell lines treated with CHIR-99021) were performed. Integrated multi-omics analysis of 31 malignancies revealed divergent dysregulation of GSK3 isoforms: GSK3\u03b1 was upregulated in 19 solid tumors but suppressed in AML, while GSK3\u03b2 was elevated in 23 cancers and high-risk AML subtypes (FAB-M0\/M1,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0013). GSK3\u03b2 outperformed GSK3\u03b1 as a pan-cancer diagnostic biomarker, achieving superior AUC in 9 tumors. Prognostically, high GSK3\u03b1 predicted poor OS in ACC (HR\u2009=\u20098.80,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0047) and MESO (HR\u2009=\u20092.75,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.0067), whereas GSK3\u03b2 independently stratified cytogenetic-risk AML (HR\u2009=\u20094.22,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.007). Immune profiling uncovered isoform-specific TME modulation: GSK3\u03b1 correlated with protumorigenic immune infiltration (Treg\/Th17, r\u2009=\u20090.38), contrasting GSK3\u03b2\u2019s broad negative associations with cytotoxic effectors (r\u2009=\u2009\u22120.27). Functional validation in AML THP-1 cells demonstrated that the GSK3 inhibitor CHIR-99021 (10 \u03bcM) significantly suppressed proliferation, induced apoptosis, and caused S-phase cell cycle arrest, concomitant with downregulation of c-Myc. These findings establish GSK3\u03b2 as a key regulator of oncogenic programs in AML. This study provides a comprehensive pan-cancer atlas of GSK3 isoform-specific functionality, nominating GSK3\u03b2 as a high-priority therapeutic target.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0344994","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:32:24Z","timestamp":1774978344000},"page":"e0344994","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["GSK3\u03b2 as a potential regulator in AML: A pan-cancer multi-omics analysis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8564-3746","authenticated-orcid":true,"given":"Ruyi","family":"Qiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8297-4745","authenticated-orcid":true,"given":"Zhejiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"issue":"1","key":"pone.0344994.ref001","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12943-023-01725-x","article-title":"Roles of tumor-associated macrophages in anti-PD-1\/PD-L1 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