{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T03:07:52Z","timestamp":1788750472087,"version":"build-2803163510"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have transformed cutaneous melanoma therapy, yet 50% of patients show primary or acquired resistance, and current biomarkers (PD-L1 and tumor mutational burden) lack precision. High-frequency ultrasound (HFUS), contrast-enhanced ultrasound (CEUS), and shear-wave elastography (SWE) are inexpensive and repeatable, but their relationship to the immune transcriptome and ICI outcomes is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this single-center retrospective study, 218 patients with cutaneous melanoma who received first-line anti-PD-1-based ICIs and pretreatment ultrasound were divided into training (n = 153) and internal validation (n = 65) sets. HFUS\/CEUS\/SWE radiomic features were filtered for reproducibility and selected by LASSO to construct an ultrasound radiomic score (US-score). Across three public transcriptomic cohorts (TCGA-SKCM, GSE91061, and GSE78220) and a melanoma single-cell dataset (GSE115978), we combined differential expression, WGCNA, immune deconvolution, and LASSO-Cox to derive an IRGS. Four core genes (CXCL10, CD8A, IFNG, and CXCL9) were validated\n                      <jats:italic>in vitro<\/jats:italic>\n                      by RT-PCR in three ATCC melanoma cell lines after IFN-\u03b3 stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The objective response rate was 42.7% (median follow-up 28.4\u00a0months). The US-score independently predicted response (adjusted OR: 2.6; 95% CI: 1.7\u20133.9; validation AUC: 0.78). The IRGS stratified public cohorts into immune-hot\/cold groups with distinct outcomes (TCGA-SKCM overall-survival HR: 2.14; 95% CI: 1.56\u20132.93; response AUC: 0.79). The US-score correlated with the IRGS (r = 0.58) and with CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell density on multiplex immunohistochemistry (r = 0.62). The combined nomogram outperformed any single biomarker (validation AUC: 0.88 vs. 0.78 [US], 0.76 [IRGS], and 0.68 [clinical]) with good calibration and net benefit and separated progression-free survival (median: 18.6 vs. 6.3 months; HR: 3.12, 95% CI: 2.08\u20134.68).\n                      <jats:italic>In vitro<\/jats:italic>\n                      , all four genes were significantly induced by IFN-\u03b3 (CXCL10 up to 8.3-fold; all\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ultrasound radiomics encodes information about the melanoma tumor-immune microenvironment; combined with an immune-related gene signature, it provides a non-invasive, biologically anchored tool for stratifying ICI response and resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1920615","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T02:19:16Z","timestamp":1788747556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound radiomics integrated with an immune-related gene signature for predicting response and resistance to immune checkpoint inhibitors in cutaneous melanoma: a retrospective radiogenomic study with biological validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jinyu","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Ultrasound, Shanghai Concord Medical Cancer Center","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Surgery VIII (Dermatology and Sores), Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Ze","sequence":"additional","affiliation":[{"name":"Department of Surgery VIII (Dermatology and Sores), Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Nanqiao Town Community Health Service Center","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1172\/JCI91190","article-title":"IFN-\u03b3-related mRNA profile predicts clinical response to PD-1 blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J. 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