Abstract
Changes in microRNA (miRNA) expression may lead to cancer development and/or contribute to its progression; however, their role in uterine sarcomas is poorly understood. Uterine sarcomas (US) belong to a rare class of heterogeneous tumors, representing about 1% of all gynecologic neoplasms. This study aimed to assess the expression profile of 84 cancer-related miRNAs and to evaluate their correlation with clinical pathological features. Eighty-two formalin-fixed paraffin-embedded (FFPE) samples were selected. In leiomyosarcoma (LMS), there was an association of lower cancer-specific survival (CSS) with the downregulation of miR-125a-5p and miR-10a-5p, and the upregulation of miR-196a-5p and miR-34c-5p. In carcinosarcoma (CS), lower CSS was associated with the upregulation of miR-184, and the downregulation of let-7b-5p and miR-124. In endometrial stromal sarcomas (ESS), the upregulation of miR-373-3p, miR-372-3p, and let-7b-5p, and the down-expression of let-7f-5p, miR-23-3p, and let-7b-5p were associated with lower CSS. Only miR-138-5p upregulation was associated with higher survival rates. miR-335-5p, miR-301a-3p, and miR-210-3p were more highly expressed in patients with tumor metastasis and relapse. miR-138-5p, miR-146b-5p, and miR-218-5p expression were associated with higher disease-free survival (DFS) in treated patients. These miRNAs represent potential prediction markers for prognosis and treatment response in these tumors.
Highlights
Uterine sarcomas (US) belong to a rare class of heterogeneous tumors comprising 3–7% of all malignancies in the uterus, representing about 1% of all gynecologic tumors [1]
For formalin-fixed paraffin-embedded (FFPE) sample analysis, we distributed the uterine sarcomas in four groups: The LMS group was composed of 37 patients with ages ranging from 32 to 91 years old; the CS group was composed of 23 patents with ages ranging from 54 to 87 years old; the endometrial stromal sarcomas (ESS) group had 18 patients with ages ranging from 27 to 82 years old; and two patients were included in the ADS group with ages ranging from 68 to 72 years old
For the CS patients, we found that three miRNAs showed association with cancer-specific survival (CSS) (Figure 3). miR-184 upregulation and let-7b-5p and miR-124-3p down regulation showed association with a lower CSS
Summary
Uterine sarcomas (US) belong to a rare class of heterogeneous tumors comprising 3–7% of all malignancies in the uterus, representing about 1% of all gynecologic tumors [1]. The US were histologically classified into uterine carcinosarcoma (CS; called malignant mixed Müllerian tumors (MMMT), uterine leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and undifferentiated sarcomas [1,3]. CS have been reclassified as a metaplastic form of endometrial carcinoma; this tumor is still included in several studies of mesenchymal tumors and in the 2014 World Health Organization (WHO) US classification [4]. Mesenchymal tumors are divided into LMS (63%), ESS (21%; usually divided into low-grade (LG-ESS) and high grade (HG-ESS), adenosarcomas (ADS, 5%), high grade undifferentiated sarcomas (5%), and other rare subtypes [5]. We included CS samples for comparison with sarcomas samples considering their mesenchymal component
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