Morelli Maria Beatrice, Amantini Consuelo, Rossi de Vermandois Jacopo Adolfo, Gubbiotti Marilena, Giannantoni Antonella, Mearini Ettore, Maggi Federica, Nabissi Massimo, Marinelli Oliviero, Santoni Matteo, Cimadamore Alessia, Montironi Rodolfo, Santoni Giorgio
School of Pharmacy, Section of Experimental Medicine, University of Camerino, 62032 Camerino, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
Cancers (Basel). 2021 Nov 28;13(23):5989. doi: 10.3390/cancers13235989.
PD-L1 represents a crucial immune checkpoint molecule in the tumor microenvironment, identified as a key target for cancer immunotherapy. A correlation between and EMT-related genes expression in various human cancers has been suggested.
By ScreenCell filtration, digital droplet PCR and confocal microscopy analysis, we aimed to investigate the expression of and EMT/invasive genes (, , , ) in circulating tumor cells (CTCs) collected from the blood of non-muscle-invasive bladder cancer (NMIBC) patients, assessing the prognostic value of these biomarkers in the disease. Welchs' test and Mann-Whitney U test, correlation index, Kaplan-Meier, Univariate and Multivariate Cox hazard proportional analysis were used.
Higher , and mRNA levels were found in pT1 compared to pTa NMIBC. As evaluated by Kaplan-Meier and Univariate and Multivariate Cox analysis, enhancement of , and expression reduces the recurrent free survival in NMIBC patients.
High , and mRNAs mark the recurrent-NMIBC patients and by reducing the RFS represent negative prognostic biomarkers in these patients.
程序性死亡受体配体1(PD-L1)是肿瘤微环境中的一种关键免疫检查点分子,被确定为癌症免疫治疗的关键靶点。已有研究表明,其与多种人类癌症中上皮-间质转化(EMT)相关基因的表达存在关联。
通过ScreenCell过滤、数字液滴PCR和共聚焦显微镜分析,我们旨在研究从非肌层浸润性膀胱癌(NMIBC)患者血液中收集的循环肿瘤细胞(CTC)中程序性死亡受体配体1(PD-L1)及EMT/侵袭相关基因(波形蛋白(VIM)、锌指E盒结合蛋白1(ZEB1)、锌指蛋白SIP1(ZEB2)、Twist同源物1(TWIST1))的表达情况,评估这些生物标志物在该疾病中的预后价值。采用韦尔奇检验、曼-惠特尼U检验、相关指数、卡普兰-迈耶分析、单因素和多因素Cox风险比例分析。
与pTa期NMIBC相比,pT1期患者的程序性死亡受体配体1(PD-L1)、波形蛋白(VIM)和锌指E盒结合蛋白1(ZEB1)的mRNA水平更高。通过卡普兰-迈耶分析以及单因素和多因素Cox分析评估,程序性死亡受体配体1(PD-L1)、波形蛋白(VIM)和锌指E盒结合蛋白1(ZEB1)表达的增强会降低NMIBC患者的无复发生存率。
程序性死亡受体配体1(PD-L1)、波形蛋白(VIM)和锌指E盒结合蛋白1(ZEB1)的高mRNA水平可作为复发性NMIBC患者的标志物,且通过缩短无复发生存期,表明这些患者存在负性预后生物标志物。