{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:31:09Z","timestamp":1787567469427,"version":"build-2736575974"},"reference-count":27,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82172690"],"award-info":[{"award-number":["82172690"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82172690"],"award-info":[{"award-number":["82172690"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82472799"],"award-info":[{"award-number":["82472799"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82472799"],"award-info":[{"award-number":["82472799"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Human pheochromocytomas and paragangliomas (PPGLs) exhibit substantial molecular and immune heterogeneity, complicating risk assessment and treatment. Here, we define three distinct tumor transcriptional subtypes (C1, C2, and C3) in a clinically annotated cohort of PPGL patients through integrative transcriptomic and immunogenomic profiling. C1 is characterized by hypoxia-driven pathways and an immunosuppressive microenvironment, correlating with poor prognosis. C2 exhibits a highly inflamed immune landscape with robust CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration, suggesting potential sensitivity to immunotherapy. C3 is enriched in metabolic reprogramming pathways and displays intermediate clinical outcomes. Genetic analysis reveals subtype-specific mutational patterns, with pseudohypoxic driver mutations (\n                    <jats:italic>SDHB<\/jats:italic>\n                    ,\n                    <jats:italic>VHL<\/jats:italic>\n                    ,\n                    <jats:italic>SDHA<\/jats:italic>\n                    , and\n                    <jats:italic>SDHD<\/jats:italic>\n                    ) predominant in C1 and C3, while kinase pathway alterations (\n                    <jats:italic>NF1<\/jats:italic>\n                    and\n                    <jats:italic>RET<\/jats:italic>\n                    ) define C2. Single-nucleus RNA sequencing of human PPGL tumors further delineates immune ecosystem diversity. Notably, we identify\n                    <jats:italic>ANGPT2<\/jats:italic>\n                    ,\n                    <jats:italic>PCSK1N<\/jats:italic>\n                    , and\n                    <jats:italic>GPX3<\/jats:italic>\n                    as key subtype-specific biomarkers, with\n                    <jats:italic>ANGPT2<\/jats:italic>\n                    driving tumor progression in C1 and emerging as a potential therapeutic target. Our findings provide a refined molecular classification integrating immune and genomic features in human PPGLs, offering a framework for improved prognostication and precision therapies in this rare neuroendocrine tumor type.\n                  <\/jats:p>","DOI":"10.7554\/elife.107108","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T14:30:27Z","timestamp":1758551427000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.107108","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional subtypes on immune microenvironment and predicting postoperative recurrence and metastasis in human pheochromocytoma and paraganglioma"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7968-3403","authenticated-orcid":true,"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034haf133","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Institute, The First Hospital 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University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Zhenfu","family":"Gao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034haf133","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Institute, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"software","vocabulary":"credit"}]},{"given":"Fengrui","family":"Nan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034haf133","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Institute, The First Hospital of Jilin University","place":["Changchun, 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