{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T07:15:59Z","timestamp":1776669359479,"version":"3.51.2"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":108,"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"}],"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>\n                      Transient receptor potential (TRP) channels regulate Ca\n                      <jats:sup>2+<\/jats:sup>\n                      homeostasis and tumor malignant phenotypes, whereas their prognostic relevance and therapeutic implications in glioblastoma (GBM) remain poorly characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We curated a comprehensive compendium of 522 TRP\u2010related genes from MSigDB, KEGG, and GeneCards. Differential expression analysis across clinical variables in The Cancer Genome Atlas Glioblastoma cohort (TCGA\u2010GBM;\n                      <jats:italic>n<\/jats:italic>\n                      = 529) identified 193 TRP\u2010associated genes significantly linked to patient outcomes. Using univariate Cox regression followed by LASSO\u2010Cox regularization, we developed a seven\u2010gene transient receptor potential\u2010related prognostic risk score (TRPRS). The model was rigorously validated in three independent external cohorts. Integrated multiomics analyses encompassed genomic alterations, tumor immune microenvironment profiling, and drug sensitivity prediction. Functional validation focused on the top\u2010ranked gene, IFNGR2, using in vitro glioma models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TRPRS robustly stratified GBM patients into high\u2010 and low\u2010risk groups with significantly distinct overall survival across all four datasets (AUC = 0.72\u20130.81). Genomically, high\u2010TRPRS tumors were enriched for PTEN loss and 9q21.3 amplification, whereas low\u2010TRPRS tumors frequently harbored TP53 mutations and 1q21.3 deletions. High TRPRS was associated with diminished cytotoxic T\u2010cell infiltration and predicted resistance to multiple therapeutics\u2014including cisplatin, carmustine, gefitinib, buparlisib, and afatinib. Notably, TIDE analysis revealed significantly reduced likelihood of response to immune checkpoint blockade in high\u2010TRPRS GBM, a pattern consistently observed in immunotherapy\u2010treated cohorts of melanoma, renal cell carcinoma, and bladder cancer. Functional assays demonstrated that IFNGR2 knockdown suppressed glioma cell proliferation and attenuated NF\u2010\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B signaling, underscoring its role as a key driver within the TRP network.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>TRPRS provides a robust, biologically grounded tool for simultaneous prognostication and therapy guidance in GBM, highlighting TRP signaling as a therapeutic vulnerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/7039302","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T06:34:47Z","timestamp":1776666887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Stratification and Subtyping of Glioblastoma 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Channels"],"prefix":"10.1155","volume":"2026","author":[{"given":"Runfeng","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4755-5444","authenticated-orcid":false,"given":"Zhichao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8873-732X","authenticated-orcid":false,"given":"Ziheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-6092","authenticated-orcid":false,"given":"Suyin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8653-7948","authenticated-orcid":false,"given":"Jingwei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2022.5359"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15072116"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14102412"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002470"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.5603\/RPOR.a2022.0113"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.12.015"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2022.03.030"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.944452"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1014834"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-08200-8"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010420"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01464-x"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74519"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-022-00304-1"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-022-10038-z"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2023.101974"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120582"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-022-01312-x"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15913"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.025328"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12091261"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14051176"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2022.136512"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02556-4"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119671"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429354659250320051057"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.2174\/0118761429385248250409060550"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmp.2025.09.002"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1260780"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-25-2237"}],"container-title":["Human 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