{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:19:14Z","timestamp":1787663954468,"version":"build-2736575974"},"reference-count":86,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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":["Cancer Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Breast cancer (BC) is a heterogeneous malignancy with diverse molecular subtypes and variable clinical outcomes. Despite diagnostic and therapeutic advances, recurrence and metastasis contribute to poor prognosis in subsets of patients. Regulators of G protein signaling (RGS) proteins, negative modulators of G protein\u2010coupled receptor (GPCR) pathways, influence tumor progression, but their expression profiles, genomic alterations, immune associations, and prognostic roles in BC remain incompletely understood. This study systematically investigated the RGS family to identify potential biomarkers and therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic and clinical data from TCGA and seven independent GEO datasets were evaluated. A random\u2010effects meta\u2010analysis established cross\u2010cohort expression consensus. Diagnostic value was assessed via ROC curve analysis. A prognostic signature was constructed using LASSO and multivariate Cox regression. Genomic alterations, DNA methylation, immune mapping, and pharmacogenomic profiling (DepMap\/Broad Institute) were comprehensively analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Meta\u2010analysis identified eight robustly dysregulated RGS genes across BC cohorts. A combined 8\u2010gene panel demonstrated diagnostic accuracy (AUC\u2009=\u20090.98). Furthermore, a LASSO\u2010derived 6\u2010gene signature successfully stratified patients into high\u2010 and low\u2010risk prognostic groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Immune infiltration profiling, validated by scRNA\u2010seq, confirmed that\n                      <jats:italic>RGS18<\/jats:italic>\n                      expression is robustly correlated with immune cells and originates predominantly from the tumor microenvironment rather than malignant cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study identifies the RGS gene family as a multidimensional framework for BC stratification. Through meta\u2010analysis, we confirmed that\n                      <jats:italic>RGS3<\/jats:italic>\n                      and\n                      <jats:italic>RGS4<\/jats:italic>\n                      act as independent oncogenic risk factors, while\n                      <jats:italic>RGS1<\/jats:italic>\n                      and\n                      <jats:italic>RGS18<\/jats:italic>\n                      serve as key immunoregulatory biomarkers. We established a high\u2010accuracy 8\u2010gene diagnostic panel (AUC\u2009=\u20090.98) and a 6\u2010gene prognostic signature (\n                      <jats:italic>RGS1, 2, 3, 10, 16, 19<\/jats:italic>\n                      ) that independently predicts patient survival. Our findings reveal that these dysregulations are driven by genomic amplifications and CpG methylation. These results position the RGS family as robust clinical biomarkers and actionable targets for precision oncology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72115","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T21:07:00Z","timestamp":1785272820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>RGS<\/scp>\n                    Family Remodeling in Breast Cancer: A Meta\u2010Analysis and Multi\u2010Omics Profiling of Prognostic Biomarkers"],"prefix":"10.1002","volume":"15","author":[{"given":"Zohreh","family":"Mirzaei","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madiheh Mazaheri","family":"Moghaddam","sequence":"additional","affiliation":[{"name":"Department of 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