{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:06:54Z","timestamp":1783933614951,"version":"3.55.0"},"reference-count":69,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Siriraj Research Fund","award":["R016332025"],"award-info":[{"award-number":["R016332025"]}]},{"name":"Siriraj Research Fund","award":["R016837002"],"award-info":[{"award-number":["R016837002"]}]},{"name":"Faculty of Medicine Siriraj Hospital, Mahidol University and Siriraj Foundation","award":["D004146"],"award-info":[{"award-number":["D004146"]}]},{"name":"Research Excellence Development (RED) Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma driven by the\n                      <jats:italic>EWSR1::NR4A3<\/jats:italic>\n                      fusion. Its unpredictable clinical course and lack of validated molecular prognostic tools complicate patient treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed whole-transcriptome targeted RNA sequencing (TempO-Seq) on archival formalin-fixed paraffin-embedded (FFPE) tumor specimens from 12 molecularly confirmed EMC cases. To explore potential biological markers, the cohort was stratified into good-prognosis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a06; overall survival (OS) &gt;8 years) and poor-prognosis (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a06; OS &lt; 8 years) groups. We conducted differential expression analysis, gene set enrichment analysis (GSEA), and applied least absolute shrinkage and selection operator (LASSO)\u2013Cox regression with bootstrap validation (1,000 iterations). Candidate genes were cross-validated using 31 external EMC cases across public microarray and NGS datasets. Immune infiltration was estimated computationally and spatially validated\n                      <jats:italic>via<\/jats:italic>\n                      multiplex immunofluorescence (mIF) on two representative specimens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 550 differentially expressed genes and derived a three-gene prognostic candidate (\n                      <jats:italic>PXN, TYMS, H1FX<\/jats:italic>\n                      ) that stratified patients by overall survival in the training cohort (log-rank\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0099), despite internal validation indicating model overfitting.\n                      <jats:italic>H1FX<\/jats:italic>\n                      was significantly upregulated in EMC versus other cartilaginous tumors across independent datasets (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001). Immune profiling revealed higher B-cell infiltration in low-risk tumors (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.005). Proof-of-concept mIF in two specimens suggested a spatially localized immunosuppressive microenvironment in the high-risk tumor, with increased exhausted CD3\n                      <jats:sup>+<\/jats:sup>\n                      CD8\n                      <jats:sup>+<\/jats:sup>\n                      PD1\n                      <jats:sup>+<\/jats:sup>\n                      T cells (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a06.4\u00a0\u00d7\u00a010\n                      <jats:sup>\u22125<\/jats:sup>\n                      ), FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      regulatory T cells (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.006), and elevated PXN protein expression (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.008). All mIF comparisons are within-specimen region of interest (ROI) analyses and should be interpreted as hypothesis-generating.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This integrated transcriptomic and spatial immune characterization identifies\n                      <jats:italic>PXN, TYMS,<\/jats:italic>\n                      and\n                      <jats:italic>H1FX<\/jats:italic>\n                      as exploratory EMC biomarker candidates, with\n                      <jats:italic>PXN<\/jats:italic>\n                      showing the most consistent cross-platform support. Immune microenvironment heterogeneity in EMC warrants further investigation. Given the small cohort and model overfitting, these findings are exploratory. Prospective validation in larger, multi-center cohorts is required.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.21497","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:24:24Z","timestamp":1783931064000},"page":"e21497","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic biomarkers for enhanced risk stratification in extraskeletal myxoid chondrosarcoma: a retrospective cohort study"],"prefix":"10.7717","volume":"14","author":[{"given":"Amphun","family":"Chaiboonchoe","sequence":"first","affiliation":[{"name":"Siriraj Center of Research Excellence for Precision Medicine and Systems Pharmacology, Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jantappapa","family":"Chanthercrob","sequence":"additional","affiliation":[{"name":"Siriraj Center of Research Excellence for 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