{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:59:47Z","timestamp":1787061587641,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":97,"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\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"publisher","award":["Y-Gilead2024-PT-0092"],"award-info":[{"award-number":["Y-Gilead2024-PT-0092"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018904","name":"Beijing Xisike Clinical Oncology Research Foundation","doi-asserted-by":"publisher","award":["WKJ-ZJ-2305"],"award-info":[{"award-number":["WKJ-ZJ-2305"]}],"id":[{"id":"10.13039\/100018904","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2024BZ20004"],"award-info":[{"award-number":["2024BZ20004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Radiotherapy resistance limits colorectal cancer (CRC) treatment efficacy, with only 15%\u201320% of patients achieving a complete response. Validated biomarkers predicting treatment response and serving as therapeutic targets are critically needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed integrative multiomics analysis of 200 CRC patients (GSE87211) with independent validation in 58 patients (GSE46862). Single\u2010cell RNA sequencing of 63,689 cells (GSE132465) determined cell\u2010type\u2010specific expression. Functional validation was conducted in radiotherapy\u2010resistant CRC cell lines through loss\u2010of\u2010function experiments including proliferation, migration\/invasion, and radiosensitivity assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FKBP10 emerged as the only gene achieving statistical significance in both discovery (log2FC = 0.74,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0007) and validation (log2FC = 0.52,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.032) cohorts among 48 radioresistance\u2010associated genes. Single\u2010cell profiling revealed that FKBP10 was predominantly expressed in cancer\u2010associated fibroblasts (CAFs, 51.5% of stromal cells), implicating CAF\u2010mediated stromal remodeling in resistance. FKBP10 knockdown significantly inhibited proliferation, colony formation (35%\u201340% reduction), migration (30%), and invasion (50%), while markedly enhancing radiosensitivity through increased DNA damage (\n                      <jats:italic>\u03b3<\/jats:italic>\n                      H2AX foci increased twofold,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01) and strand breaks (comet tail DNA: 22%\u2009\u2192\u200943%,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This multiomics study establishes FKBP10 as a robust CAF\u2010derived biomarker and functional therapeutic target for radiotherapy resistance in CRC, providing a foundation for developing FKBP10\u2010targeted combination strategies for precision cancer treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/3905052","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:39:02Z","timestamp":1775716742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative Multiomics and Single\u2010Cell Analyses Identify FKBP10 as a Predictor of Radiotherapy Outcome in Colorectal 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