Kim Wun-Jae, Bae Suk-Chul
Department of Urology, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea.
Cancer Sci. 2008 Apr;99(4):646-52. doi: 10.1111/j.1349-7006.2008.00735.x.
Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression, and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by the conventional clinical and pathological parameters. None of the biomarkers reported to date have shown sufficient sensitivity and specificity for detecting the whole spectrum of bladder cancer diseases in routine clinical practice. The limitations of established prognostic markers requires us to identify better molecular parameters that could be of interest in predicting the prognosis of bladder cancer patients, in particular, the high-risk patient groups that are at risk of progression and recurrence. Recent progress in epigenetic modification and gene silencing opened a new avenue for the identification of epigenetic markers, which appears to be more useful for cancer diagnosis and prognosis. Although epigenetic markers also have limitations, the combined epigenetic marker approach may increase sensitivity and reliability. The epigenetic silencing of tumor-suppressor genes is interesting from a clinical standpoint because of the possibility of reversing epigenetic changes and restoring gene function in a cell. In addition, microarray technology provides us with additional tools for the analysis of global gene-expression analysis of tumor samples. Future microarray analyses are likely to reveal particular gene-expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as a patient's survival and responsiveness to different anticancer therapies, with great specificity and sensitivity.
膀胱癌是由异质性细胞群体组成的,许多因素可能参与决定其复发、进展以及患者的生存情况。对于任何具有重要临床相关性的候选预后标志物而言,它必须具备超越传统临床和病理参数的预测能力。迄今为止报道的生物标志物中,没有一种在常规临床实践中对检测膀胱癌的全谱表现出足够的敏感性和特异性。现有预后标志物的局限性要求我们识别出更优的分子参数,这些参数对于预测膀胱癌患者的预后,尤其是对于有进展和复发风险的高危患者群体可能具有重要意义。表观遗传修饰和基因沉默方面的最新进展为表观遗传标志物的识别开辟了一条新途径,表观遗传标志物似乎在癌症诊断和预后方面更有用。尽管表观遗传标志物也有局限性,但联合表观遗传标志物方法可能会提高敏感性和可靠性。从临床角度来看,肿瘤抑制基因的表观遗传沉默很有意思,因为存在逆转表观遗传变化并恢复细胞中基因功能的可能性。此外,微阵列技术为我们提供了额外的工具,用于分析肿瘤样本的全局基因表达。未来的微阵列分析可能会揭示特定的基因表达特征,这些特征能够以高度的特异性和敏感性预测膀胱癌进展和复发的可能性、患者的生存情况以及对不同抗癌疗法的反应。