{"doi":"10.1210/clinem/dgaf269","title":"The USP8 Mutational Status in Combination With Postsurgical Cortisol Levels for Predicting Recurrence of Cushing Disease","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:sec>\n                    <jats:title>Context</jats:title>\n                    <jats:p>The ubiquitin-specific protease 8 (USP8) gene mutations are the most common driver changes in Cushing disease (CD). However, few studies have investigated the association between USP8 mutation and recurrence, and the results have been inconclusive.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>To identify the predictors of recurrence and evaluate the prognostic role of USP8 mutation.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>One hundred and seven patients with pathologically confirmed corticotroph adenomas were included. Somatic USP8 mutations were identified using Sanger sequencing. Recurrence predictors were estimated using multivariate Cox models, followed by receiver operating characteristic curves and Kaplan–Meier analysis.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>Thirteen patients (12.6%) experienced recurrence, with a mean follow-up period of 65 months after surgery. The recurrence rate was significantly higher in USP8-mutated tumors than in USP8 wildtype tumors (26.5% vs 5.8%; P = .009). Multivariate Cox models revealed that USP8 mutation, high postsurgical morning serum cortisol (MSC), and high 1-mg dexamethasone suppression test (DST) were associated with an increased 5-year recurrence risk. Furthermore, Kaplan–Meier survival analysis showed that patients with USP8 mutation, combined with either high postsurgical MSC (&amp;gt;2.5 μg/dL) or high 1-mg DST (&amp;gt;0.78 μg/dL), were more prone to recurrence (log-rank P &amp;lt; .001). The negative predictive values were 98% and 100%, while the positive predictive values improved from 33% to 55% and from 47% to 86%, respectively.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>Our study corroborates USP8 mutational status in combination with postsurgical MSC or 1-mg DST as independent predictors of long-term remission, highlighting their potential role in stratifying patients at risk for suboptimal outcomes.</jats:p>\n                  </jats:sec>","journal":"The Journal of Clinical Endocrinology &amp; Metabolism","year":2025,"id":637647,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1655801,"name":"Sichang Zheng","orcid":null,"position":1,"is_corresponding":false},{"id":865907,"name":"Lei Ye","orcid":"0000-0002-6529-6178","position":2,"is_corresponding":false},{"id":1655805,"name":"Tingwei Su","orcid":null,"position":3,"is_corresponding":false},{"id":572842,"name":"Jing Xie","orcid":"0000-0002-5065-7911","position":4,"is_corresponding":false},{"id":1424086,"name":"Lei Jiang","orcid":"0000-0002-6365-1965","position":5,"is_corresponding":false},{"id":1254586,"name":"Yiran Jiang","orcid":"0000-0003-2078-8125","position":6,"is_corresponding":false},{"id":51250,"name":"Xu Zhong","orcid":"0000-0001-5138-3724","position":7,"is_corresponding":false},{"id":1655812,"name":"Luming Wu","orcid":null,"position":8,"is_corresponding":false},{"id":1655815,"name":"Wenzhong Zhou","orcid":null,"position":9,"is_corresponding":false},{"id":942888,"name":"Weiqing Wang","orcid":"0000-0001-6027-3084","position":10,"is_corresponding":false},{"id":1450826,"name":"Weiwei Zhou","orcid":"0000-0003-2003-7743","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The USP8 Mutational Status in Combination With Postsurgical Cortisol Levels for Predicting Recurrence of Cushing Disease","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:sec>\n                    <jats:title>Context</jats:title>\n                    <jats:p>The ubiquitin-specific protease 8 (USP8) gene mutations are the most common driver changes in Cushing disease (CD). However, few studies have investigated the association between USP8 mutation and recurrence, and the results have been inconclusive.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>To identify the predictors of recurrence and evaluate the prognostic role of USP8 mutation.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>One hundred and seven patients with pathologically confirmed corticotroph adenomas were included. Somatic USP8 mutations were identified using Sanger sequencing. Recurrence predictors were estimated using multivariate Cox models, followed by receiver operating characteristic curves and Kaplan–Meier analysis.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>Thirteen patients (12.6%) experienced recurrence, with a mean follow-up period of 65 months after surgery. The recurrence rate was significantly higher in USP8-mutated tumors than in USP8 wildtype tumors (26.5% vs 5.8%; P = .009). Multivariate Cox models revealed that USP8 mutation, high postsurgical morning serum cortisol (MSC), and high 1-mg dexamethasone suppression test (DST) were associated with an increased 5-year recurrence risk. Furthermore, Kaplan–Meier survival analysis showed that patients with USP8 mutation, combined with either high postsurgical MSC (&amp;gt;2.5 μg/dL) or high 1-mg DST (&amp;gt;0.78 μg/dL), were more prone to recurrence (log-rank P &amp;lt; .001). The negative predictive values were 98% and 100%, while the positive predictive values improved from 33% to 55% and from 47% to 86%, respectively.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>Our study corroborates USP8 mutational status in combination with postsurgical MSC or 1-mg DST as independent predictors of long-term remission, highlighting their potential role in stratifying patients at risk for suboptimal outcomes.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40424186","pmcid":null,"openalex_id":"https://openalex.org/W4410772059","authors":[],"funders":[{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFC2501600","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFC2501601","title":null},{"funder_name":"National Key Research and Development Program of China","grant_id":"2021YFC2501603","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"91857205","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81400779","title":null},{"funder_name":"Noncommunicable Chronic Diseases-National Science and Technology","grant_id":"2023ZD0517900","title":null},{"funder_name":"Chinese Society of Endocrinology","grant_id":"13050890474","title":null},{"funder_name":"Shanghai Shenkang Hospital Development Center","grant_id":"SHDC2020CR2002A","title":null},{"funder_name":"Shanghai Shenkang Hospital Development Center","grant_id":"SHDC2020CR6015","title":null},{"funder_name":"Shanghai Municipal Commission of Health and Family Planning","grant_id":"201840049","title":null},{"funder_name":"Shanghai Medical and Health Development Foundation","grant_id":"","title":null}],"total_grants":11,"fwci":3.9059,"citation_percentile":0.94381585,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":5}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgaf269/63373437/dgaf269.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jcem/article-pdf/111/1/e156/63373437/dgaf269.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/clinem/dgaf269","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40424186","host_type":"repository"}],"fields_of_study":["Pituitary Gland Disorders and Treatments","Adrenal and Paraganglionic Tumors","Myasthenia Gravis and Thymoma"],"mesh_terms":["Adenoma","Adult","Female","Follow-Up Studies","Humans","Hydrocortisone","Male","Middle Aged","Mutation","Neoplasm Recurrence, Local","Endopeptidases","Prognosis","Ubiquitin Thiolesterase","Pituitary ACTH Hypersecretion","ACTH-Secreting Pituitary Adenoma","Young Adult","Endosomal Sorting Complexes Required for Transport"],"keywords":["Internal medicine","Sanger sequencing","Context (archaeology)","Cushing's disease","Medicine","Proportional hazards model","Mutation","Oncology","Multivariate analysis","Gastroenterology","Disease","Gene","Biology","Genetics","Recurrence","Predictors","Transsphenoidal Surgery","Cushing Disease","Usp8 Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T19:17:11.859707Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}