Usha S Polaki, Trey E Gilpin, Apoorva T Patil, Emily Chiu, Ruth Baker, Peng Liu, Tatiana S Pavletich, Morteza Seifi, Paula M Mañán-Mejías, Jordan Morrissey, Jenna Port, Rene Welch Schwartz, Irene M Ong, Dina El-Rayes, Mahmoud A Khalifa, Pei Hui, Vanessa L Horner, María Virumbrales-Muñoz, Britt K Erickson, Lisa Barroilhet, Stephanie M McGregor, Emery H Bresnick, Daniel R Matson
{"title":"Loss of GATA2 Promotes Invasion and Predicts Cancer Recurrence and Survival in Uterine Serous Carcinoma.","authors":"Usha S Polaki, Trey E Gilpin, Apoorva T Patil, Emily Chiu, Ruth Baker, Peng Liu, Tatiana S Pavletich, Morteza Seifi, Paula M Mañán-Mejías, Jordan Morrissey, Jenna Port, Rene Welch Schwartz, Irene M Ong, Dina El-Rayes, Mahmoud A Khalifa, Pei Hui, Vanessa L Horner, María Virumbrales-Muñoz, Britt K Erickson, Lisa Barroilhet, Stephanie M McGregor, Emery H Bresnick, Daniel R Matson","doi":"10.1172/jci.insight.187073","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>A priori knowledge of recurrence risk in patients with non-metastatic (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.</p><p><strong>Methods: </strong>GATA2 expression was scored by immunohistochemistry (IHC) across a retrospective multi-institutional 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 hazards 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.</p><p><strong>Results: </strong>Patients with FIGO stage I GATA2high USCs had 100% recurrence-free and 100% cancer related survival, which was significantly better than patients with GATA2low USCs. In patients for whom adjuvant chemotherapy was omitted, patients with GATA2high USC had 100% recurrence free 5-year survival compared to 60% recurrence free survival in patients with GATA2low USC. Depletion of GATA2 in patient-derived USC cells increased invasion in vitro.</p><p><strong>Conclusions: </strong>Routine GATA2 IHC identifies 33% of FIGO stage I USC patients who have a greatly reduced risk of post-hysterectomy 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 likely improve outcomes in USC patients.</p><p><strong>Funding: </strong>NIH 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.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.3000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCI insight","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1172/jci.insight.187073","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: A priori knowledge of recurrence risk in patients with non-metastatic (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.
Methods: GATA2 expression was scored by immunohistochemistry (IHC) across a retrospective multi-institutional 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 hazards 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.
Results: Patients with FIGO stage I GATA2high USCs had 100% recurrence-free and 100% cancer related survival, which was significantly better than patients with GATA2low USCs. In patients for whom adjuvant chemotherapy was omitted, patients with GATA2high USC had 100% recurrence free 5-year survival compared to 60% recurrence free survival in patients with GATA2low USC. Depletion of GATA2 in patient-derived USC cells increased invasion in vitro.
Conclusions: Routine GATA2 IHC identifies 33% of FIGO stage I USC patients who have a greatly reduced risk of post-hysterectomy 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 likely improve outcomes in USC patients.
Funding: NIH 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.
期刊介绍：
JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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