{"doi":"10.1093/ejendo/lvaf097","title":"Prevalence and clinical associations of <i>USP8</i> variants in corticotroph tumours: a systematic review and aggregate data meta-analysis of 2171 cases","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Objective</jats:title>\n                  <jats:p>Somatic USP8 variants are common in corticotroph tumours, but their reported prevalence and association with clinical characteristics vary widely among publications.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Aim</jats:title>\n                  <jats:p>To determine the prevalence and clinical relevance of USP8 variants based on published evidence.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Design and methods</jats:title>\n                  <jats:p>We conducted a systematic review and meta-analysis of existing literature. We used PubMed, Embase, and Web of Science databases. The inclusion criteria were original studies including ≥5 patients with Cushing's disease reporting genetic USP8 status. The exclusion criteria were no human research, unclear USP8 information, and case reports (&amp;lt;5 patients). A random-effects model meta-analysis and meta-regression were conducted. Studies reporting functional corticotroph tumours and also silent/non-functioning tumours were not excluded.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>From 6782 extracted records, 44 studies summarizing 51 records were included in our meta-analysis (total n = 2171 cases, 692 with USP8 variants). Pooled prevalence was 31.1% (95% CI, 26.5%-36.0%) and was higher in cases with functional tumours (34.1%; 95% CI, 29.4%–39.1%). Patients with USP8 variants were mostly female (odds ratios [OR] 4.52, 95% CI, 3.39-6.02) and in average 4.47 years younger at diagnosis (95% CI, 2.28-6.65 years younger). USP8 status was associated with higher odds for postoperative remission (OR 1.76, 95% CI, 1.18-2.63) and recurrence (OR 2.38, 95% CI, 1.03-5.48). There was no clear evidence of association with any other clinical or tumour variable included in our analysis, mostly due to heterogeneity among studies. Meta-regression analysis showed that the variability in the prevalence of USP8 variants among studies was related to female/male ratio (adjusted R2 = 0.301), but not to other variables, such as tumour size or invasion.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>The present meta-analysis shows that patients with USP8 variant tumours are mostly female, diagnosed at younger age, more likely to achieve postoperative remission, but at a higher risk of recurrence than those with tumours carrying the reference allele.</jats:p>\n               </jats:sec>","journal":"European Journal of Endocrinology","year":2025,"id":638764,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"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":1659315,"name":"Vivian von Selzam","orcid":null,"position":1,"is_corresponding":false},{"id":1659316,"name":"Prajina Sharma","orcid":null,"position":2,"is_corresponding":false},{"id":58343,"name":"Martín Reincke","orcid":"0000-0002-9817-9875","position":3,"is_corresponding":false},{"id":616737,"name":"Marily Theodoropoulou","orcid":"0000-0002-7378-4374","position":4,"is_corresponding":false},{"id":1659314,"name":"Luis G Perez-Rivas","orcid":"0000-0002-2555-0602","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Prevalence and clinical associations of <i>USP8</i> variants in corticotroph tumours: a systematic review and aggregate data meta-analysis of 2171 cases","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Objective</jats:title>\n                  <jats:p>Somatic USP8 variants are common in corticotroph tumours, but their reported prevalence and association with clinical characteristics vary widely among publications.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Aim</jats:title>\n                  <jats:p>To determine the prevalence and clinical relevance of USP8 variants based on published evidence.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Design and methods</jats:title>\n                  <jats:p>We conducted a systematic review and meta-analysis of existing literature. We used PubMed, Embase, and Web of Science databases. The inclusion criteria were original studies including ≥5 patients with Cushing's disease reporting genetic USP8 status. The exclusion criteria were no human research, unclear USP8 information, and case reports (&amp;lt;5 patients). A random-effects model meta-analysis and meta-regression were conducted. Studies reporting functional corticotroph tumours and also silent/non-functioning tumours were not excluded.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Results</jats:title>\n                  <jats:p>From 6782 extracted records, 44 studies summarizing 51 records were included in our meta-analysis (total n = 2171 cases, 692 with USP8 variants). Pooled prevalence was 31.1% (95% CI, 26.5%-36.0%) and was higher in cases with functional tumours (34.1%; 95% CI, 29.4%–39.1%). Patients with USP8 variants were mostly female (odds ratios [OR] 4.52, 95% CI, 3.39-6.02) and in average 4.47 years younger at diagnosis (95% CI, 2.28-6.65 years younger). USP8 status was associated with higher odds for postoperative remission (OR 1.76, 95% CI, 1.18-2.63) and recurrence (OR 2.38, 95% CI, 1.03-5.48). There was no clear evidence of association with any other clinical or tumour variable included in our analysis, mostly due to heterogeneity among studies. Meta-regression analysis showed that the variability in the prevalence of USP8 variants among studies was related to female/male ratio (adjusted R2 = 0.301), but not to other variables, such as tumour size or invasion.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions</jats:title>\n                  <jats:p>The present meta-analysis shows that patients with USP8 variant tumours are mostly female, diagnosed at younger age, more likely to achieve postoperative remission, but at a higher risk of recurrence than those with tumours carrying the reference allele.</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40392165","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"314061271-TRR 205","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://academic.oup.com/ejendo/advance-article-pdf/doi/10.1093/ejendo/lvaf097/63244155/lvaf097.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/ejendo/article-pdf/192/6/S41/63244155/lvaf097.pdf","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Pituitary Neoplasms","Ubiquitin Thiolesterase","Endopeptidases","Prevalence","Female","Male","Endosomal Sorting Complexes Required for Transport"],"keywords":["ACTH","Meta-analysis","Cushing's Disease","Genetic Variant","Usp8","Cortisol Corticotroph Tumour"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T21:25:02.682219Z","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":[]}