Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of Endometrial Stromal Sarcomas, Uterine Tumors Resembling Ovarian Sex Cord Tumors, and Undifferentiated Uterine Sarcomas With Prognostic Insights

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10498451" target="_blank" >RIV/00179906:_____/25:10498451 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/27661989:_____/25:10002995 RIV/00216224:14110/25:00141740 RIV/00216208:11110/25:10498451 RIV/00216208:11120/25:43928474 a 10 dalších

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lDWHtfrjQJ" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=lDWHtfrjQJ</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.labinv.2025.104198" target="_blank" >10.1016/j.labinv.2025.104198</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of Endometrial Stromal Sarcomas, Uterine Tumors Resembling Ovarian Sex Cord Tumors, and Undifferentiated Uterine Sarcomas With Prognostic Insights

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of Endometrial Stromal Sarcomas, Uterine Tumors Resembling Ovarian Sex Cord Tumors, and Undifferentiated Uterine Sarcomas With Prognostic Insights

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30214 - Obstetrics and gynaecology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Laboratory Investigation

ISSN

0023-6837

e-ISSN

1530-0307

Svazek periodika

105

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

104198

Kód UT WoS článku

001517898700001

EID výsledku v databázi Scopus

2-s2.0-105008247620