文章：

肿瘤分期、预后和治疗选择的生物标志物

Biomarkers in Cancer Staging, Prognosis and Treatment Selection

原文发布日期：2005-10-01

DOI: 10.1038/nrc1739

类型: Review Article

开放获取: 否

要点：

1. The TNM staging system (based on a combination of tumour size or depth (T), lymph node spread (N), and presence or absence of metastases (M)) provides a basis for prediction of survival, choice of initial treatment, stratification of patients in clinical trials, accurate communication among healthcare providers, and uniform reporting of the end result of cancer management.
2. There is a dilemma in TNM staging: frequent revisions to include new biomarkers would undermine the value conferred by the stability and universality of TNM, but a static formulation of TNM risks falling behind the state of the art in diagnostic techniques, biological concepts and biomarkers.
3. Biomarkers initially considered for cancer screening or risk assessment might also prove useful for cancer staging or grading.
4. A biomarker for use in staging or grading need not be as specific as it must be for screening, early detection or risk assessment.
5. As molecularly targeted cancer therapeutics become more common, assessing the intended target will more often be deemed necessary for prediction of clinical response, independent of TNM stage. Targeted therapies and their associated biomarkers will often 'co-evolve'.
6. The ideal biomarker assay for staging should be sensitive, specific, cost-effective, fast, and robust against inter-operator and inter-institutional variability. It must also demonstrate clinical value beyond that of the other types of information that are already available at the time of diagnosis.
7. Biomarker candidates must undergo clinical validation before receiving US Food and Drug Administration approval. For most candidate markers, that process is just beginning.
8. Despite all of the potentially useful biomarkers — for example, those identified from microarray or mass spectrometry studies — almost none have been incorporated into formal TNM staging.

要点翻译：

1. TNM分期系统（基于肿瘤大小或浸润深度（T）、淋巴结转移（N）以及远处转移（M）的组合）为生存预测、初始治疗方案选择、临床试验患者分层、医疗人员间的精准沟通以及癌症治疗结果的标准化报告提供了基础。
2. TNM分期面临一个两难困境：频繁修订以纳入新生物标志物会削弱其稳定性和普适性带来的价值，但固守不变的分期方案又可能落后于诊断技术、生物学概念和生物标志物的前沿发展。
3. 最初考虑用于癌症筛查或风险评估的生物标志物，可能后来被证明对癌症分期或分级也有价值。
4. 用于分期或分级的生物标志物，其特异性无需达到筛查、早期检测或风险评估所要求的高度。
5. 随着分子靶向癌症疗法日益普及，为预测临床反应，评估靶向治疗的目标指标将更常被视为必要步骤，这与TNM分期无关。靶向疗法及其相关生物标志物往往会“协同进化”。
6. 用于分期的理想生物标志物检测应具备高敏感性、高特异性、成本效益高、快速，并能抵抗操作者间和机构间差异的影响。此外，它还必须展现出超越诊断时已获其他信息的临床价值。
7. 候选生物标志物必须经过临床验证才能获得美国食品药品监督管理局的批准。对大多数候选标志物而言，这一过程才刚刚开始。
8. 尽管存在大量潜在有用的生物标志物（例如通过微阵列或质谱分析研究发现的标志物），但几乎没有任何标志物被正式纳入TNM分期系统。

英文摘要：

Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Their use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. However, translation from bench to bedside outside of the research setting has proved more difficult than might have been expected. Understanding how and when biomarkers can be integrated into clinical care is crucial if we want to translate the promise into reality.

摘要翻译： 

基因组学、蛋白质组学和分子病理学的进展催生了许多具有潜在临床价值的候选生物标志物。它们若在诊断时用于癌症分期和个体化治疗，有望改善患者照护。然而，从实验室到临床的转化，在研究领域之外，却比预期更为艰难。若要将这一前景变为现实，关键在于理解生物标志物何时以及如何能被整合进临床照护之中。

原文链接：

Biomarkers in Cancer Staging, Prognosis and Treatment Selection