Avgeris Margaritis, Mavridis Konstantinos, Tokas Theodoros, Stravodimos Konstantinos, Fragoulis Emmanuel G, Scorilas Andreas
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece and First Department of Urology, "Laiko" General Hospital, Medical School, University of Athens, Agiou Thoma 17, 11527 Athens, Greece.
First Department of Urology, "Laiko" General Hospital, Medical School, University of Athens, Agiou Thoma 17, 11527 Athens, Greece.
Carcinogenesis. 2015 May;36(5):528-37. doi: 10.1093/carcin/bgv024. Epub 2015 Mar 24.
Accurate prognosis is a key factor in establishing optimal therapeutic decisions; yet in the case of bladder cancer (BlCa) current prognostic indicators cannot ensure optimal disease management. Here, we aimed to evaluate the previously unexplored clinical potential of the urological cancer-related miR-145, miR-143 and miR-224 in BlCa. A total of 279 bladder tissue specimens were included in this study (133 BlCa, 107 adjacent normal and 39 healthy samples). Total RNA was extracted from tissues, it was polyadenylated and reverse transcribed to cDNA. The expression of target molecules was measured via quantitative real-time PCR. The expression levels of both miR-143 and miR-145 were significantly decreased, whereas those of miR-224 were increased in BlCa. Receiver operating characteristic curve analysis indicated a significant discriminatory capacity for miR-143/miR-145 levels. Important associations with disease aggressiveness were observed for all three microRNAs; elevated levels were observed in tumors of higher stage and grade, as well as in 'high-risk' TaT1 patients. More importantly, high miR-143/145 levels could effectively prognose inferior overall survival for muscle-invasive patients and could independently predict the progression of superficial tumors. Finally, the combination of miR-143/145 overexpression with the widely used prognostic markers of European Organization for Research and Treatment of Cancer-risk groups or recurrence at the first follow-up cystoscopy resulted to a superior positive prediction of non-muscle-invasive bladder cancer short-term progression compared with the use of the abovementioned markers alone. The cancer-related miR-143, miR-145 and miR-224 were investigated for the first time in the clinical setting of BlCa, and miR-143/145 cluster constitutes a novel marker helpful for providing an enhanced prediction of oncologic outcome for BlCa patients.
准确的预后是做出最佳治疗决策的关键因素；然而，对于膀胱癌（BlCa）而言，目前的预后指标无法确保实现最佳的疾病管理。在此，我们旨在评估泌尿系统癌症相关的miR-145、miR-143和miR-224在膀胱癌中尚未被探索的临床潜力。本研究共纳入279份膀胱组织标本（133份膀胱癌标本、107份癌旁正常标本和39份健康样本）。从组织中提取总RNA，进行多聚腺苷酸化并逆转录为cDNA。通过定量实时PCR检测靶分子的表达。在膀胱癌中，miR-143和miR-145的表达水平均显著降低，而miR-224的表达水平升高。受试者工作特征曲线分析表明，miR-143/miR-145水平具有显著的鉴别能力。观察到所有这三种 microRNA 与疾病侵袭性均存在重要关联；在更高分期和分级的肿瘤以及“高危”TaT1患者的肿瘤中观察到水平升高。更重要的是，高miR-143/145水平能够有效预测肌层浸润性患者较差的总生存期，并且能够独立预测浅表肿瘤的进展。最后，与单独使用上述标志物相比，miR-143/145过表达与欧洲癌症研究与治疗组织风险组广泛使用的预后标志物或首次随访膀胱镜检查时的复发相结合，对非肌层浸润性膀胱癌的短期进展具有更高的阳性预测价值。首次在膀胱癌的临床背景下研究了癌症相关的miR-143、miR-145和miR-224，并且miR-143/145簇构成了一种新型标志物，有助于增强对膀胱癌患者肿瘤学结局的预测。
