A cautionary note on the evaluation of biomarkers of subtypes of a single disease.
A cautionary note on the evaluation of biomarkers of subtypes of a single disease.
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关于评估单一疾病亚型生物标志物的警告。
DOI：
10.1093/aje/kwn183
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发表时间：
2008
影响因子：
5
通讯作者：
Yasui,Yutaka
中科院分区：
文献类型：
--
作者：
Adewale,AdeniyiJ;Liu,Qi;Dinu,Irina;Lampe,PaulD;Mitchell,BreeL;Yasui,Yutaka
疾病分子特征的异质性给试图识别疾病生物标志物的研究人员提出了挑战。在生物标志物发现工作之前，在异质疾病组内进行分层，相当于将疾病病例分组为更同质的亚型，似乎是发现亚型特异性生物标志物的自然策略。这是因为生物学上更同质的亚组可能比整个异质疾病组更容易与非疾病组区分开来。使用乳腺癌蛋白质生物标志物发现项目的示例说明了这种两步方法的误导性好处。使用条件概率论证来解释该框架中潜在的分析陷阱。
Heterogeneity in the molecular characteristics of a disease presents a challenge to investigators attempting to identify biomarkers of the disease. Preceding the biomarker discovery effort with stratification within a heterogeneous disease group, which amounts to grouping disease cases into more homogeneous subtypes, seems to be a natural strategy for discovering subtype-specific biomarkers. This is because biologically more homogeneous subgroups are presumably easier to distinguish from the nondiseased than the entire heterogeneous disease group. The misleading benefits of this two-step approach are illustrated using an example from a protein biomarker discovery project for breast cancer. A potential analytical pitfall in this framework is explained using a conditional probability argument.