Kugler Karl G, Hackl Werner O, Mueller Laurin Aj, Fiegl Heidi, Graber Armin, Pfeiffer Ruth M
Institute for Bioinformatics and Translational Research, University for Health Sciences, Medical Informatics and Technology, EWZ 1, 6060, Hall in Tirol, Austria.
J Clin Bioinforma. 2011 Mar 8;1:9. doi: 10.1186/2043-9113-1-9.
Using serum, plasma or tumor tissue specimens from biobanks for biomarker discovery studies is attractive as samples are often readily available. However, storage over longer periods of time can alter concentrations of proteins in those specimens. We therefore assessed the bias in estimates of association from case-control studies conducted using banked specimens when maker levels changed over time for single markers and also for multiple correlated markers in simulations. Data from a small laboratory experiment using serum samples guided the choices of simulation parameters for various functions of changes of biomarkers over time. RESULTS: In the laboratory experiment levels of two serum markers measured at sample collection and again in the same samples after approximately ten years in storage increased by 15%. For a 15% increase in marker levels over ten years, odds ratios (ORs) of association were significantly underestimated, with a relative bias of -10%, while for a 15% decrease in marker levels over time ORs were too high, with a relative bias of 20%. CONCLUSION: Biases in estimates of parameters of association need to be considered in sample size calculations for studies to replicate markers identified in exploratory analyses.
利用生物样本库中的血清、血浆或肿瘤组织标本进行生物标志物发现研究很有吸引力，因为样本通常很容易获得。然而，长时间储存会改变这些标本中蛋白质的浓度。因此，我们评估了在模拟中单个标志物以及多个相关标志物的水平随时间变化时，使用储存标本进行的病例对照研究中关联估计的偏差。一项使用血清样本的小型实验室实验数据指导了生物标志物随时间变化的各种函数模拟参数的选择。结果：在实验室实验中，在样本采集时测量的两种血清标志物水平，以及在储存约十年后的同一样本中再次测量时，增加了15%。对于标志物水平在十年内增加15%的情况，关联的优势比（OR）被显著低估，相对偏差为-10%，而对于标志物水平随时间下降15%的情况，OR过高，相对偏差为20%。结论：在样本量计算中需要考虑关联参数估计的偏差，以便进行研究以复制在探索性分析中确定的标志物。
