Epithelial-mesenchymal transition associated markers in sarcomatoid transformation of clear cell renal cell carcinoma

IF 2.8 4区 医学 Q2 PATHOLOGY Experimental and molecular pathology Pub Date : 2024-06-13 DOI:10.1016/j.yexmp.2024.104909
Tanja Čugura, Emanuela Boštjančič, Sara Uhan, Nina Hauptman, Jera Jeruc
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Abstract

Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development and progression of many cancers. Partial EMT (pEMT) could represent a critical step in tumor migration and dissemination. Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of renal cell carcinoma (RCC) composed of a carcinomatous (sRCC-Ca) and sarcomatous (sRCC-Sa) component. The role of (p)EMT in the progression of RCC to sRCC remains unclear. The aim of this study was to investigate the involvement of (p)EMT in RCC and sRCC. Tissue samples from 10 patients with clear cell RCC (ccRCC) and 10 patients with sRCC were selected. The expression of main EMT markers (miR-200 family, miR-205, SNAI1/2, TWIST1/2, ZEB1/2, CDH1/2, VIM) was analyzed by qPCR in ccRCC, sRCC-Ca, and sRCC-Sa and compared to non-neoplastic tissue and between both groups. Expression of E-cadherin, N-cadherin, vimentin and ZEB2 was analyzed using immunohistochemistry. miR-200c was downregulated in sRCC-Ca compared to ccRCC, while miR-200a was downregulated in sRCC-Sa compared to ccRCC. CDH1 was downregulated in sRCC-Sa when compared to any other group. ZEB2 was downregulated in ccRCC and sRCC compared to corresponding non-neoplastic kidney. A positive correlation was observed between CDH1 expression and miR-200a/b/c. Our results suggest that full EMT is not present in sRCC. Instead, discreet molecular differences exist between ccRCC, sRCC-Ca, and sRCC-Sa, possibly representing distinct intermediary states undergoing pEMT.

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透明细胞肾细胞癌肉瘤样转化中的上皮-间质转化相关标记物
上皮-间质转化(EMT)在许多癌症的发生和发展过程中起着至关重要的作用。部分 EMT(pEMT)可能是肿瘤迁移和扩散的关键步骤。肉瘤样肾细胞癌(sRCC)是一种侵袭性肾细胞癌(RCC),由癌(sRCC-Ca)和肉瘤(sRCC-Sa)成分组成。目前还不清楚(p)EMT在RCC向sRCC发展过程中的作用。本研究旨在探讨(p)EMT在RCC和sRCC中的参与情况。研究选取了10例透明细胞RCC(ccRCC)患者和10例sRCC患者的组织样本。通过qPCR分析了ccRCC、sRCC-Ca和sRCC-Sa中主要EMT标记物(miR-200家族、miR-205、SNAI1/2、TWIST1/2、ZEB1/2、CDH1/2、VIM)的表达情况,并与非肿瘤组织以及两组之间进行了比较。与ccRCC相比,miR-200c在sRCC-Ca中下调,而与ccRCC相比,miR-200a在sRCC-Sa中下调。与其他组别相比,CDH1在sRCC-Sa中下调。与相应的非肿瘤性肾脏相比,ZEB2在ccRCC和sRCC中被下调。CDH1的表达与miR-200a/b/c呈正相关。我们的研究结果表明,sRCC 并不存在完全的 EMT。相反,ccRCC、sRCC-Ca 和 sRCC-Sa 之间存在着不同的分子差异,这可能代表了进行 pEMT 的不同中间状态。
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来源期刊
CiteScore
8.90
自引率
0.00%
发文量
78
审稿时长
11.5 weeks
期刊介绍: Under new editorial leadership, Experimental and Molecular Pathology presents original articles on disease processes in relation to structural and biochemical alterations in mammalian tissues and fluids and on the application of newer techniques of molecular biology to problems of pathology in humans and other animals. The journal also publishes selected interpretive synthesis reviews by bench level investigators working at the "cutting edge" of contemporary research in pathology. In addition, special thematic issues present original research reports that unravel some of Nature''s most jealously guarded secrets on the pathologic basis of disease. Research Areas include: Stem cells; Neoangiogenesis; Molecular diagnostics; Polymerase chain reaction; In situ hybridization; DNA sequencing; Cell receptors; Carcinogenesis; Pathobiology of neoplasia; Complex infectious diseases; Transplantation; Cytokines; Flow cytomeric analysis; Inflammation; Cellular injury; Immunology and hypersensitivity; Athersclerosis.
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