Laboratory investigation; a journal of technical methods and pathology. 2025 May 24:104198. doi: 10.1016/j.labinv.2025.104198
Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of ESS, UTROSCT, and UUS with Prognostic Insights
262例子宫肉瘤的分子分型：基于RNA测序的ESS、UTR和UUS聚类及其预后意义 翻译改进
Jan Hojný 1, Jiří Dvořák 2, Romana Vránková 2, Michaela Kendall Bártů 2, Nikola Hájková 2, Eva Krkavcová 2, Miroslava Flídrová 2, Ivana Stružinská 2, Kristýna Němejcová 2, Jiří Bouda 3, Květoslava Michalová 4, David Cibula 5, Renata Poncová 5, Janusz Rys 6, Mariusz Ksiazek 7, Marcin Jędryka 8, Tymoteusz Poprawski 9, Alberto Berjon 10, Ignacio Zapardiel 10, Jan Laco 11, Munachiso Ndukwe 11, Jaroslav Klát 12, Vladimír Židlík 13, Zoard Krasznai 14, Robert Poka 14, Michal Zikán 15, Zuzana Špůrková 16, Magdalena Bizoń 17, Włodzimierz Sawicki 18, Nataliya Volodko 19, Iryna Yezhova 19, Francesca Ciccarone 20, Giulia Zinicola 20, Marcin Bobiński 21, Marta Ostrowska-Leśko 22, Ivan Franin 23, Mirela Kekić 24, Tetiana Piatnytska 25, Ihor Varchak 25, Radovan Pilka 26, Radim Marek 26, Jitka Hausnerová 27, Michaela Koblížková 28, Pavel Havelka 29, Vladimír Kalist 29, Maciej Stukan 30, Karolina Grabowska 31, Georgína Kolníková 32, Milan Krkoška 33, Michael Halaška 34, Jana Drozenová 35, Simona Stolnicu 36, Mihai Capilna 36, Archil Sharashenidze 37, Miranda Gudadze 37, Radoslav Matěj 35, Pavel Dundr 38
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作者单位
1 Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. Electronic address: jan.hojny@vfn.cz.2 Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.3 Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, Charles University and University Hospital in Pilsen, Pilsen, Czech Republic.4 Department of Pathology, Faculty of Medicine in Pilsen, Charles University and Bioptical Laboratory, Ltd, Pilsen, Czech Republic.5 Department of Gynaecology, Obstetrics and Neonatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic.6 Department of Tumor Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow branch, Krakow, Poland.7 Department of Tumor Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Cracow branch, Krakow, Poland; Department of Pathology, University Hospital Crosshouse, Kilmarnock, Scotland.8 Department of Gynecological Oncology, Wroclaw Medical University, Wroclaw, Poland.9 Department of Oncological Gynecology, Lower Silesian Oncology, Pulmonology and Hematology Center, Wroclaw, Poland.10 Pathology Department, La Paz University Hospital, Madrid, Spain.11 The Fingerland Department of Pathology, Charles University Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.12 Oncogynecologic Center, Department of Obstetrics and Gynecology, University Hospital and University of Ostrava, Ostrava, Czech Republic.13 Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czech Republic.14 Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.15 Department of Gynecology and Obstetrics, First Faculty of Medicine, Charles University and University Hospital Bulovka, Prague, Czech Republic.16 Department of Pathology, University Hospital Bulovka, Prague, Czech Republic.17 LUX MED Oncology Hospital, Warsaw, Poland; Chair and Department of Obstetrics, Gynaecology and Gynaecological Oncology, Medical University of Warsaw, Warsaw, Poland.18 Chair and Department of Obstetrics, Gynaecology and Gynaecological Oncology, Medical University of Warsaw, Warsaw, Poland.19 Lviv Regional Oncological Center, Department of Oncology and Radiology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.20 Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.21 Chair and Department of Oncologic Gynecology and Gynecology, Medical University of Lublin, Lublin, Poland.22 Chair and Department of Toxicology, Medical University of Lublin, Lublin, Poland.23 Ljudevit Jurak Department of Pathology and Cytology, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia.24 Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia.25 Department of Gynecologic Oncology, Khmelnytskyi Regional Antitumor Center, Khmelnytskyi, Ukraine.26 University Hospital Olomouc, Czech Republic.27 Department of Pathology, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.28 Department of Obstetrics and Gynecology, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.29 Tomas Bata Regional Hospital, Zlín, Czech Republic.30 Departament of Gynecologic Oncology, Pomeranian Hospitals, Gdynia, Poland; Medical University of Gdansk, Surgical Oncology Clinic, Gdynia, Poland.31 Departament of Gynecologic Oncology, Pomeranian Hospitals, Gdynia, Poland.32 Department of Pathology, National Oncology Institute, Bratislava, Slovakia.33 Department of Gynecologic Oncology, National Oncology Institute, Bratislava, Slovakia.34 Department of Obstetrics and Gynaecology, Third Medical Faculty, Charles University in Prague and University Hospital Kralovske Vinohrady, Prague, Czech Republic.35 Department of Pathology, University Hospital Kralovske Vinohrady, Prague, Czech Republic.36 University of Medicine, Pharmacy, Sciences and Technology GE Palade, Targu Mures, Romania.37 Caucasus Medical Centre, Tbilisi, Georgia.38 Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. Electronic address: pavel.dundr@vfn.cz.
DOI: 10.1016/j.labinv.2025.104198 PMID: 40419088
摘要 中英对照阅读
Low-grade endometrial stromal sarcomas (LG-ESS), high-grade endometrial stromal sarcomas (HG-ESS), undifferentiated uterine sarcomas (UUS), and uterine tumors resembling ovarian sex cord tumors (UTROSCT) are distinct non-smooth muscle cell neoplasms with varying clinical outcomes often exhibiting overlapping characteristics. Diagnosis can be supported by identifying characteristic recurrent translocations, which may be absent in some cases, complicating the distinction of equivocal cases. Additionally, cases with overlapping features of LG and HG characteristics are recognized. To address these challenges, we analyzed RNA-Seq profiles of 262 cases. Our results revealed that LG-ESS, with and without recurrent fusions, clustered into two partially overlapping expression profiles associated with distinct overall and relapse-free survival outcomes, with the cluster containing a majority of fusion-negative tumors demonstrating better prognoses. UTROSCT expression profiles closely resembled those of both LG-ESS subgroups, with NCOA3 fusion-positive cases clustering in groups with better survival outcomes. Furthermore, a distinct cluster for HG-ESS with BCOR and YWHAE fusions was identified, differentiating these tumors from HG-ESS without fusions. ONECUT3 emerged as a potential specific marker for this HG-ESS-fusion entity. A significant expression overlap was observed between monomorphic HG-ESS without fusions and pleomorphic UUS. These samples separated further into two mixed clusters distinguished by differences in immune activity, which significantly influenced overall survival and relapse-free survival outcomes. Unsupervised clustering of UUS revealed subgroups resembling either HG-ESS or muscle-cell differentiated tumors, suggesting that UUS may include poorly differentiated distinct entities, such as leiomyosarcoma, and that the distinction from HG-ESS may, in some cases, be arbitrary. Our transcriptome analysis highlights several entities with distinct survival characteristics, providing a foundation for further characterization of these rare, often difficult-to-classify, tumors.
Keywords: ESS; HG-ESS; LG-ESS; ONECUT3; RNA-Seq; UTROSCT; UUS; endometrial stromal sarcomas; expression profiling; undifferentiated uterine sarcomas; uterine tumor resembling ovarian sex cord tumors.
Copyright © 2025. Published by Elsevier Inc.
Keywords：molecular landscape; uterine sarcomas; RNA-Seq clustering; prognostic insights
低级别子宫内膜间质肉瘤（LG-ESS）、高级别子宫内膜间质肉瘤（HG-ESS）、未分化子宫肉瘤（UUS）和类似卵巢性索肿瘤的子宫肿瘤（UTROSCT）是一组不同类型的非平滑肌细胞肿瘤，具有不同的临床结局，并且这些肿瘤往往表现出重叠的特点。通过识别特征性的反复发生的染色体易位可以支持诊断，但有些病例可能没有这些特征，这使得难以区分一些不明确的情况。此外，还存在一些同时具备低级别和高级别特点的案例。为了应对这些挑战，我们分析了262个样本的RNA-Seq谱型。我们的研究结果表明，无论是带有还是不带反复发生的融合基因的LG-ESS都聚集在两个部分重叠的表达谱中，它们与不同的总生存期和无复发生存期相关，其中包含大多数非融合肿瘤的那一簇预后较好。UTROSCT的表达谱与两种LG-ESS亚群中的任意一种都很相似，带有NCOA3融合基因的案例集中在有更好生存结果的组别内。此外，我们确定了一个具有BCOR和YWHAE融合基因的独特HG-ESS聚类，从而将这些肿瘤与其他无融合基因的HG-ESS区分开来。ONECUT3成为这种HG-ESS融合实体的一个潜在特异性标记物。在没有融合基因的同质性高级别子宫内膜间质肉瘤与未分化子宫肉瘤之间观察到了显著的表达重叠现象，这些样本进一步划分为两个混合聚类，并且根据免疫活性的不同而区分，这显著影响了总生存期和无复发生存期结果。对UUS进行非监督式聚类分析揭示了类似于HG-ESS或平滑肌细胞分化肿瘤的亚群，暗示UUS可能包含类似平滑肌肉瘤等较差分化的独立实体，并且在某些情况下，与HG-ESS的区别可能是任意的。我们的转录组分析强调了几种具有不同生存特征的实体，为这些罕见且难以分类的肿瘤进一步研究提供了基础。
关键词：
ESS；HG-ESS；LG-ESS；ONECUT3；RNA-Seq；UTROSCT；UUS；子宫内膜间质肉瘤；表达谱分析；未分化子宫肉瘤；类似卵巢性索肿瘤的子宫肿瘤
版权所有 © 2025。Elsevier Inc.出版。
关键词：分子图谱; 子宫肉瘤; RNA测序聚类; 预后洞察
Copyright © Laboratory investigation; a journal of technical methods and pathology. 中文内容为AI机器翻译，仅供参考！
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