■上皮-间质转化(EMT)在膀胱癌(BC)的侵袭和转移中起重要作用。研究表明,由于EMT相关编程的不同,肌肉侵入性BC(MIBC)和非MIBC(NMIBC)在分子水平上是不同的。最近的研究表明,特定miRNA的失调与BC中的EMT有关。在这样的背景下,我们旨在研究一系列MIBCs和NMIBCs中EMT标记的免疫表达及其与miRNA-200c表达的相关性。
■对50例经尿道膀胱肿瘤电切术(TURBT)获得的尿BC进行定量实时聚合酶链反应,以定量miR-200c的表达,膀胱切除术标本,和十个肿瘤周围的膀胱组织。ZEB1,ZEB2,TWIST,E-cadherin,对肿瘤和肿瘤周围膀胱组织进行β-catenin。
■评估了35个TURBT和15个膀胱切除术标本。在MIBC中,E-cadherin表达缺失(72.3%),β-连环蛋白(66.7%),ZEB1、ZEB2和TWIST2的免疫反应性为53.3%,86.7%,73.3%的病例,分别。在NMIBC中,E-cadherin表达缺失(22.5%),β-连环蛋白(17.1%)和ZEB1,ZEB2和TWIST免疫反应性在11.5%,51.4%,91.4%的病例,分别。在保留E-钙粘蛋白和阴性TWIST表达的情况下,注意到miRNA-200c的上调。miRNA-200c表达的下调在所有显示E-cadherin丢失的病例中被注意到,β-连环蛋白,并且在MIBC中对ZEB1,ZEB2和TWIST具有免疫反应性的情况下。在具有保留的β-连环蛋白和那些对ZEB1和ZEB2免疫阴性的MIBC的情况下,也注意到miRNA-200c表达的下调。NMIBC也有类似的趋势。与肿瘤周围膀胱组织相比,在高级别和低级别NMIBC中miRNA-200c的中值表达较低,并且没有统计学意义。
■这项研究首次探讨了miR200C与E-cadherin的关系,B-catenin,以及它的直接转录调节因子,即Zeb1,Zeb2和Twist在BC的同一队列中。我们观察到miRNA-200c在MIBC和NMIBC中均下调。我们在显示miR200Cs下调的BC病例中鉴定了TWIST的新表达,这表明它是促成EMT的改变的miRNA-200c表达的蛋白质靶标之一,并且可以用作有前途的诊断标记和治疗靶标。高级NMIBC中E-钙黏着蛋白和ZEB1免疫表达的丧失表明其具有侵袭性临床行为。然而,ZEB2在BC中的异质表达限制了其诊断和预后的效用。
UNASSIGNED: Epithelial-mesenchymal transition (EMT) plays an important role in bladder carcinoma (BC) invasiveness and metastasis. Studies have shown that muscle-invasive BC (MIBC) and non-MIBC (NMIBC) are different at the molecular level owing to different EMT-related programming. Recent studies suggest that dysregulation of specific miRNAs is linked to EMT in BC. With this background, we aimed to
study the immunoexpression of EMT-markers and its correlation with miRNA-200c expression in a series of MIBCs and NMIBCs.
UNASSIGNED: Quantitative real-time-polymerase chain reaction for the quantification of miR-200c expression was performed on 50 cases of urinary BC obtained from transurethral resection of bladder tumor (TURBT), cystectomy specimens, and ten peritumoral bladder tissue. Immunohistochemistry for ZEB1, ZEB2, TWIST, E-cadherin, and β-catenin was performed on tumor and peritumoral bladder tissue.
UNASSIGNED: Thirty-five TURBT and 15 cystectomy specimens were assessed. Among MIBC, loss of expression of E-cadherin (72.3%), β-catenin (66.7%), and ZEB1, ZEB2, and TWIST2 immunoreactivity was noted in 53.3%, 86.7%, and 73.3% of cases, respectively. Among NMIBC, loss of expression of E-cadherin (22.5%), β-catenin (17.1%) and ZEB1, ZEB2, and TWIST immunoreactivity was noted in 11.5%, 51.4%, and 91.4% of cases, respectively. Upregulation of miRNA-200c was noted in cases with retained E-cadherin and negative
TWIST expression. Downregulation of miRNA-200c expression was noted in all the cases showing loss of E-cadherin, β-catenin, and in cases immunoreactive for ZEB1, ZEB2, and TWIST in MIBC. Downregulation of miRNA-200c expression was also noted in cases of MIBC with retained β-catenin and those immunonegative for ZEB1 and ZEB2. A similar trend was noted in NMIBC. Median miRNA-200c expression was low in both high-grade and low-grade NMIBC compared to peritumoral bladder tissue and was not statistically significant.
UNASSIGNED: This
study for the first time explores the relation of miR200C with E-cadherin, b-catenin, and its direct transcriptional regulators, namely Zeb1, Zeb2, and
Twist in the same cohort of BC. We observed that miRNA-200c is downregulated in both MIBC and NMIBC. We identified novel expression of
TWIST in cases of BC showing downregulation of miR200Cs suggesting that it is one of the protein targets of altered miRNA-200c expression contributing to EMT and can serve as a promising diagnostic marker and therapeutic target. Loss of E-cadherin and ZEB1 immunoexpression in high-grade NMIBC suggests an aggressive clinical behavior. However, ZEB2 heterogeneous expression in BC limits its diagnostic and prognostic utility.