Nagata Masayoshi, Muto Satoru, Horie Shigeo
Department of Urology, Graduate School of Medicine, Juntendo University, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan.
Department of Urology, School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 117-003, Japan.
Dis Markers. 2016;2016:8205836. doi: 10.1155/2016/8205836. Epub 2016 Jan 26.
Although many clinical and molecular markers for predicting outcomes in bladder cancer (BC) have been reported, their application in clinical practice remains unclear. Bladder carcinogenesis has two distinct molecular pathways that direct the development of BC. FGFR3 mutations are common in low-grade BC, while TP53 mutation or loss of RB1 is associated with muscle-invasive BC. However, no tissue-based gene markers confirmed by prospective large-scale trials in BC have been used in clinical practice. Micro-RNA analyses of BC tissue revealed that miR-145 and miR-29c* function as tumor suppressors, whereas miR-183 and miR-17-5p function as oncogenic miRNAs. In liquid biopsy, circulating tumor cells (CTC), exosomes, or cell-free RNA is extracted from the peripheral blood samples of cancer patients to analyze cancer prognosis. It was reported that detection of CTC was associated with poor prognostic factors. However, application of liquid biopsy in BC treatment is yet to be explored. Although several cell-free RNAs, such as miR-497 in plasma or miR-214 in urine, could be promising novel circulating biomarkers, they are used only for diagnosing BC as the case that now stands. Here, we discuss the application of novel biomarkers in evaluating and measuring BC outcomes.
尽管已经报道了许多用于预测膀胱癌(BC)预后的临床和分子标志物,但其在临床实践中的应用仍不明确。膀胱癌发生有两条不同的分子途径指导膀胱癌的发展。FGFR3突变在低级别膀胱癌中常见,而TP53突变或RB1缺失与肌肉浸润性膀胱癌相关。然而,在膀胱癌中经前瞻性大规模试验证实的基于组织的基因标志物尚未应用于临床实践。对膀胱癌细胞组织进行的微小RNA分析显示,miR-145和miR-29c*起到肿瘤抑制作用,而miR-183和miR-17-5p起到致癌微小RNA的作用。在液体活检中,从癌症患者外周血样本中提取循环肿瘤细胞(CTC)、外泌体或游离RNA以分析癌症预后。据报道,CTC的检测与不良预后因素相关。然而,液体活检在膀胱癌治疗中的应用尚待探索。尽管几种游离RNA,如血浆中的miR-497或尿液中的miR-214,可能是有前景的新型循环生物标志物,但就目前情况而言,它们仅用于膀胱癌的诊断。在此,我们讨论新型生物标志物在评估和衡量膀胱癌预后中的应用。