Amantini Consuelo, Maggi Federica, Rossi de Vermandois Jacopo Adolfo, Gubbiotti Marilena, Giannantoni Antonella, Mearini Ettore, Nabissi Massimo, Tomassoni Daniele, Santoni Giorgio, Morelli Maria Beatrice
School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
Urologic and Andrologic Clinics, University of Perugia, 05100 Perugia, Italy.
Cancers (Basel). 2022 Jun 25;14(13):3118. doi: 10.3390/cancers14133118.
Bladder cancer (BC) is one of the most expensive lifetime cancers to treat because of the high recurrence rate, repeated surgeries, and long-term cystoscopy monitoring and treatment. The lack of an accurate classification system predicting the risk of recurrence or progression leads to the search for new biomarkers and strategies. Our pilot study aimed to identify a prognostic gene signature in circulating tumor cells (CTCs) isolated by ScreenCell devices from muscle invasive and non-muscle invasive BC patients. Through the PubMed database and Cancer Genome Atlas dataset, a panel of 15 genes modulated in BC with respect to normal tissues was selected. Their expression was evaluated in CTCs and thanks to the univariate and multivariate Cox regression analysis, EGFR, TRPM4, TWIST1, and ZEB1 were recognized as prognostic biomarkers. Thereafter, by using the risk score model, we demonstrated that this 4-gene signature significantly grouped patients into high- and low-risk in terms of recurrence free survival (HR = 2.704, 95% CI = 1.010−7.313, Log-rank p < 0.050). Overall, we identified a new prognostic signature that directly impacted the prediction of recurrence, improving the choice of the best treatment for BC patients.
膀胱癌（BC）是治疗成本最高的终身性癌症之一，原因在于其高复发率、反复手术以及长期的膀胱镜监测与治疗。缺乏准确的预测复发或进展风险的分类系统促使人们寻找新的生物标志物和策略。我们的初步研究旨在从肌肉浸润性和非肌肉浸润性BC患者中，通过ScreenCell设备分离出的循环肿瘤细胞（CTC）中鉴定出一种预后基因特征。通过PubMed数据库和癌症基因组图谱数据集，选择了一组在BC中相对于正常组织有表达变化的15个基因。评估了它们在CTC中的表达，并通过单变量和多变量Cox回归分析，确定表皮生长因子受体（EGFR）、瞬时受体电位阳离子通道M4（TRPM4）、TWIST1和锌指E盒结合蛋白1（ZEB1）为预后生物标志物。此后，通过使用风险评分模型，我们证明这个4基因特征在无复发生存方面能将患者显著分为高风险和低风险组（风险比=2.704，95%置信区间=1.010 - 7.313，对数秩检验p<0.050）。总体而言，我们鉴定出一种新的预后特征，它直接影响复发预测，改善了BC患者最佳治疗方案的选择。
