{"doi":"10.1172/jci.insight.187073","title":"Loss of GATA2 promotes invasion and predicts cancer recurrence and survival in uterine serous carcinoma","abstract":"BACKGROUNDA priori knowledge of recurrence risk in patients with nonmetastatic (International Federation of Gynecology and Obstetrics [FIGO] stage I) uterine serous carcinoma (USC) would enable a risk-stratified approach to the use of adjuvant chemotherapy. This would greatly reduce treatment-related morbidity and be predicted to improve survival.METHODSGATA2 expression was scored by IHC across a retrospective multiinstitutional cohort of 195 primary USCs. Associations between GATA2 levels and clinicopathologic metrics were evaluated using Student's t test, Fisher's exact test, Kaplan-Meier method, and Cox proportional hazard ratio. Invasion in patient-derived USC cells was assessed by Student's t test. RNA-Seq, anti-GATA2 ChIP-Seq, and confirmatory Western blotting enabled identification of GATA2 targets.RESULTSPatients with FIGO stage I GATA2hi USCs had 100% recurrence-free and 100% cancer-related survival, which was significantly better than patients with GATA2lo USCs. In patients for whom adjuvant chemotherapy was omitted, patients with GATA2hi USC had 100% recurrence-free 5-year survival compared with 60% recurrence-free survival in patients with GATA2lo USC. Depletion of GATA2 in patient-derived USC cells increased invasion in vitro.CONCLUSIONRoutine GATA2 IHC identifies 33% of patients with FIGO stage I USC who have a greatly reduced risk of posthysterectomy USC recurrence. Our results suggest that a GATA2-guided personalized medicine approach could be rapidly implemented in most hospital settings, would reduce treatment-related morbidity, and would likely improve outcomes in patients with USC.FUNDINGNIH grants R01 DK068634, P30 CA014520, S10 OD023526, K08 DK127244, T32 HL007899, the UW-Madison Department of Pathology and Laboratory Medicine, the UW-Madison Centennial Scholars Program, the Diane Lindstrom Foundation, the American Cancer Society, the V Foundation, The Hartwell Foundation, and the UMN Department of Obstetrics, Gynecology, and Women's Health.","journal":"JCI Insight","year":2025,"id":543579,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1433603,"name":"Trey E Gilpin","orcid":null,"position":1,"is_corresponding":false},{"id":1120038,"name":"Apoorva T. Patil","orcid":"0000-0002-6339-0419","position":2,"is_corresponding":false},{"id":681170,"name":"Emily Chiu","orcid":null,"position":3,"is_corresponding":false},{"id":1433163,"name":"R. W. R. Baker","orcid":"0000-0002-8546-1804","position":4,"is_corresponding":false},{"id":1433164,"name":"Peng Liu","orcid":"0000-0003-1749-6455","position":5,"is_corresponding":false},{"id":883645,"name":"Tatiana S. Pavletich","orcid":"0000-0002-8813-2125","position":6,"is_corresponding":false},{"id":1433165,"name":"Morteza Seifi","orcid":"0000-0001-5884-9427","position":7,"is_corresponding":false},{"id":1433604,"name":"Paula M. Mañán-Mejías","orcid":null,"position":8,"is_corresponding":false},{"id":1433605,"name":"Jordan Morrissey","orcid":null,"position":9,"is_corresponding":false},{"id":280232,"name":"Jenna Port","orcid":null,"position":10,"is_corresponding":false},{"id":1433606,"name":"Rene Welch Schwartz","orcid":null,"position":11,"is_corresponding":false},{"id":298238,"name":"Irene M. 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