{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T03:42:14Z","timestamp":1767066134258,"version":"3.48.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170806"],"award-info":[{"award-number":["82170806"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403632"],"award-info":[{"award-number":["82403632"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ30915"],"award-info":[{"award-number":["2023JJ30915"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Research Fund of National Clinical Research Center for Geriatric Disorders","award":["2022LNJJ12"],"award-info":[{"award-number":["2022LNJJ12"]}]},{"name":"Guang Dong Basic and Applied Basic Research Foundation","award":["2023A1515110998"],"award-info":[{"award-number":["2023A1515110998"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The frequency of pathogenic variants (PVs) in HRAS in Caucasian populations with pheochromocytoma and paraganglioma (PPGL) is significantly lower than that in Chinese, which reflects the ethnic difference in genetic landscape. However, the clinical and biochemical characteristics of patients with HRAS-mutant PPGL are rarely reported. This study explored the clinical and biochemical profiles of Chinese patients with HRAS-mutant PPGL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This is a retrospective analysis of clinical and biochemical characteristics of patients with PPGL (N = 717).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data on demographics, tumor characteristics, blood\/urine biochemistry, preoperative preparation, intraoperative hemodynamics, and perioperative complications were analyzed in patients with HRAS-mutant and non-HRAS PPGL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 111 (15.5%) patients were with PPGL due to PVs in HRAS. Patients with HRAS-mutant PPGL had higher plasma metanephrine levels, an increased incidence of catecholamine-associated signs and symptoms (CAS), intraoperative hemodynamic instability (IHI) and intensive care unit (ICU) transfer right after surgery compared with those with non-HRAS tumor. Despite with similar tumor size, patients with HRAS-mutant PPGL had significantly higher plasma metanephrine levels, a higher incidence of presenting CAS and IHI than those with tumors due to PVs in other genes associated with kinase pathways. A significantly high catecholamine content in HRAS-mutant PPGL was associated with high levels of enzymes of catecholamine metabolism such as tyrosine hydroxylase and phenylethanolamine N-methyltransferase, which was independent of tumor locations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with HRAS-mutant PPGL have higher plasma metanephrine levels and a higher risk of IHI and ICU transfer, which therefore requires personalized perioperative managements.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf250","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:36:36Z","timestamp":1765197396000},"page":"700-708","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and biochemical characteristics of patients with somatic\n                    <i>HRAS<\/i>\n                    -mutant pheochromocytoma and paraganglioma"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-4575","authenticated-orcid":false,"given":"Kun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]},{"name":"Fudan Institute for Metabolic Diseases, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anze","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology, First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong 510120 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1886-2613","authenticated-orcid":false,"given":"Jingjing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]},{"name":"Fudan Institute for Metabolic Diseases, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6932-333X","authenticated-orcid":false,"given":"Nicole","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden , Fetscherstrasse 74, Dresden 01307 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9267-0471","authenticated-orcid":false,"given":"Minghao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0274-4057","authenticated-orcid":false,"given":"Longfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, Hunan 410008 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"issue":"1","key":"2025122921565920500_lvaf250-B1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/s12022-022-09704-6","article-title":"Overview of the 2022 WHO classification of paragangliomas and pheochromocytomas","volume":"33","author":"Mete","year":"2022","journal-title":"Endocr Pathol"},{"key":"2025122921565920500_lvaf250-B2","doi-asserted-by":"publisher","first-page":"20420188231207544","DOI":"10.1177\/20420188231207544","article-title":"Pheochromocytoma: a changing perspective and current concepts","volume":"14","author":"Kiriakopoulos","year":"2023","journal-title":"Ther Adv Endocrinol Metab"},{"issue":"10","key":"2025122921565920500_lvaf250-B3","doi-asserted-by":"publisher","first-page":"dgaa502","DOI":"10.1210\/clinem\/dgaa502","article-title":"Sino-European differences in the genetic landscape and clinical presentation of pheochromocytoma and paraganglioma","volume":"105","author":"Jiang","year":"2020","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2025122921565920500_lvaf250-B4","doi-asserted-by":"publisher","first-page":"bvae038","DOI":"10.1210\/jendso\/bvae038","article-title":"Patient sex and origin influence distribution of driver genes and clinical presentation of paraganglioma","volume":"8","author":"Richter","year":"2024","journal-title":"J Endocr Soc"},{"issue":"2","key":"2025122921565920500_lvaf250-B5","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ccell.2017.01.001","article-title":"Comprehensive molecular characterization of pheochromocytoma and paraganglioma","volume":"31","author":"Fishbein","year":"2017","journal-title":"Cancer cell"},{"issue":"10","key":"2025122921565920500_lvaf250-B6","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1111\/j.1349-7006.1992.tb02722.x","article-title":"Ras mutations in endocrine tumors: mutation detection by polymerase chain reaction-single strand conformation polymorphism","volume":"83","author":"Yoshimoto","year":"1992","journal-title":"Jpn J Cancer Res"},{"issue":"7","key":"2025122921565920500_lvaf250-B7","doi-asserted-by":"publisher","first-page":"E1266","DOI":"10.1210\/jc.2012-4257","article-title":"Somatic mutations in H-RAS in sporadic pheochromocytoma and paraganglioma identified by exome sequencing","volume":"98","author":"Crona","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025122921565920500_lvaf250-B8","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/gcc.22347","article-title":"HRAS mutation prevalence and associated expression patterns in pheochromocytoma","volume":"55","author":"Stenman","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"key":"2025122921565920500_lvaf250-B9","doi-asserted-by":"publisher","first-page":"921645","DOI":"10.3389\/fendo.2022.921645","article-title":"Mutational profile and potential molecular therapeutic targets of pheochromocytoma","volume":"13","author":"Ma","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"12","key":"2025122921565920500_lvaf250-B10","doi-asserted-by":"publisher","first-page":"e230230","DOI":"10.1530\/ERC-23-0230","article-title":"Regulation of epinephrine biosynthesis in HRAS-mutant paragangliomas","volume":"30","author":"Li","year":"2023","journal-title":"Endocr Relat Cancer."},{"issue":"8","key":"2025122921565920500_lvaf250-B11","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1007\/s00345-014-1397-z","article-title":"Ten year experience of retroperitoneal laparoscopic resection for pheochromocytomas: a dual-centre study of 72 cases","volume":"33","author":"de Fourmestraux","year":"2015","journal-title":"World J Urol"},{"key":"2025122921565920500_lvaf250-B12","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.urology.2016.09.004","article-title":"Surgical and hemodynamic outcomes in pheochromocytoma surgery: a prospective cohort study","volume":"98","author":"Rao","year":"2016","journal-title":"Urology"},{"issue":"1","key":"2025122921565920500_lvaf250-B13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12957-019-1649-x","article-title":"Comparison of retroperitoneal laparoscopic versus open adrenalectomy for large pheochromocytoma: a single-center retrospective study","volume":"17","author":"Zhu","year":"2019","journal-title":"World J Surg Oncol"},{"issue":"6","key":"2025122921565920500_lvaf250-B14","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1002\/jcsm.13071","article-title":"Impact of body composition and genotype on haemodynamics during surgery for pheochromocytoma and paraganglioma","volume":"13","author":"Pang","year":"2022","journal-title":"J Cachexia Sarcopenia Muscle."},{"issue":"1","key":"2025122921565920500_lvaf250-B15","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1038\/s41598-021-04736-0","article-title":"Mutated RAS-associating proteins and ERK activation in relapse\/refractory diffuse large B cell lymphoma","volume":"12","author":"Benoit","year":"2022","journal-title":"Sci Rep"},{"issue":"6","key":"2025122921565920500_lvaf250-B16","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1158\/1541-7786.MCR-12-0089","article-title":"Mouse tissues that undergo neoplastic progression after K-Ras activation are distinguished by nuclear translocation of phospho-Erk1\/2 and robust tumor suppressor responses","volume":"10","author":"Parikh","year":"2012","journal-title":"Mol Cancer Res"},{"issue":"1","key":"2025122921565920500_lvaf250-B17","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1507\/endocrj.EJ19-0278","article-title":"Development and validation of a clinical model to predict intraoperative hemodynamic instability in patients with pheochromocytomas surgery","volume":"67","author":"Bai","year":"2020","journal-title":"Endocr J."},{"issue":"6","key":"2025122921565920500_lvaf250-B18","doi-asserted-by":"publisher","first-page":"101956","DOI":"10.1016\/j.beem.2024.101956","article-title":"Recent advances in algorithms predicting hemodynamic instability undergoing surgery for phaeochromocytoma and paraganglioma","volume":"38","author":"Guan","year":"2024","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"1","key":"2025122921565920500_lvaf250-B19","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1097\/JS9.0000000000001995","article-title":"Genetic background and intraoperative haemodynamic instability in patients with pheochromocytoma and paraganglioma: a multicenter retrospective study","volume":"111","author":"Li","year":"2024","journal-title":"Int J Surg"},{"issue":"1","key":"2025122921565920500_lvaf250-B20","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13045-024-01631-9","article-title":"RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms","volume":"17","author":"Yang","year":"2024","journal-title":"J Hematol Oncol"},{"issue":"1","key":"2025122921565920500_lvaf250-B21","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1038\/s41467-023-36769-6","article-title":"Genomic and immune landscape of metastatic pheochromocytoma and paraganglioma","volume":"14","author":"Calsina","year":"2023","journal-title":"Nat Commun."},{"issue":"2","key":"2025122921565920500_lvaf250-B22","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1210\/clinem\/dgac563","article-title":"Recurrent disease in patients with sporadic pheochromocytoma and paraganglioma","volume":"108","author":"Li","year":"2023","journal-title":"J Clin Endocrinol Metab."},{"issue":"9","key":"2025122921565920500_lvaf250-B23","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1002\/ijc.28868","article-title":"Opposing effects of HIF1\u03b1 and HIF2\u03b1 on chromaffin cell phenotypic features and tumor cell proliferation: insights from MYC-associated factor X","volume":"135","author":"Qin","year":"2014","journal-title":"Int J Cancer"},{"issue":"3","key":"2025122921565920500_lvaf250-B24","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s43018-020-0043-5","article-title":"Circulating tumor DNA and liquid biopsy in oncology","volume":"1","author":"Cescon","year":"2020","journal-title":"Nat Cancer"},{"issue":"3","key":"2025122921565920500_lvaf250-B25","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1016\/j.chest.2021.04.016","article-title":"Usefulness of circulating tumor DNA in identifying somatic mutations and tracking tumor evolution in patients with non-small cell lung cancer","volume":"160","author":"Roosan","year":"2021","journal-title":"Chest"},{"issue":"24","key":"2025122921565920500_lvaf250-B26","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1056\/NEJMoa2200075","article-title":"Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer","volume":"386","author":"Tie","year":"2022","journal-title":"N Engl J Med"},{"issue":"1","key":"2025122921565920500_lvaf250-B27","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s12943-018-0876-z","article-title":"Exosomal double-stranded DNA as a biomarker for the diagnosis and preoperative assessment of pheochromocytoma and paraganglioma","volume":"17","author":"Wang","year":"2018","journal-title":"Mol Cancer"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article-pdf\/doi\/10.1093\/ejendo\/lvaf250\/65823753\/lvaf250.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/193\/6\/700\/65823753\/lvaf250.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/193\/6\/700\/65823753\/lvaf250.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T02:57:07Z","timestamp":1767063427000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/193\/6\/700\/8375723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":27,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11,26]]}},"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvaf250","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"type":"print","value":"0804-4643"},{"type":"electronic","value":"1479-683X"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,11,26]]}}}