Tainsky Michael A, Chatterjee Madhumita, Levin Nancy K, Draghici Sorin, Abrams Judith
Program in Molecular Biology and Genetics, Karmanos Cancer Institute/Wayne State University, 110 E. Warren, Detroit, MI 48201.
Biomark Insights. 2007 Jul 10;2:261-7.
It has become very clear that a single molecular event is inadequate to accurately predict the biology (or pathophysiology) of cancer. Furthermore, using any single molecular event as a biomarker for the early detection of malignancy may not comprehensively identify the majority of individuals with that disease. Therefore, the fact that technologies have arisen that can simultaneously detect several, possibly hundreds, of biomarkers has propelled the field towards the development of multianalyte-based in vitro diagnostic early detection tests for cancer using body fluids such as serum, plasma, sputum, saliva, or urine. These multianalyte tests may be based on the detection of serum autoantibodies to tumor antigens, the presence of cancer-related proteins in serum, or the presence of tumor-specific genomic changes that appear in plasma as free DNA. The implementation of non-invasive diagnostic approaches to detect early stage cancer may provide the physician with evidence of cancer, but the question arises as to how the information will affect the pathway of clinical intervention. The confirmation of a positive result from an in vitro diagnostic cancer test may involve relatively invasive procedures to establish a true cancer diagnosis. If in vitro diagnostic tests are proven to be both specific, i.e. rarely produce false positive results due to unrelated conditions, and sufficiently sensitive, i.e. rarely produce false negative results, then such screening tests offer the potential for early detection and personalized therapeutics using multiple disease-related targets with convenient and non-invasive means. Here we discuss the technical and regulatory barriers inherent in development of clinical multianalyte biomarker assays.
很明显，单一分子事件不足以准确预测癌症的生物学特性（或病理生理学）。此外，将任何单一分子事件用作恶性肿瘤早期检测的生物标志物可能无法全面识别大多数患有该疾病的个体。因此，能够同时检测几种甚至可能数百种生物标志物的技术的出现推动了该领域朝着开发基于多种分析物的体外诊断早期癌症检测测试的方向发展，这些测试使用血清、血浆、痰液、唾液或尿液等体液。这些多种分析物测试可能基于对肿瘤抗原的血清自身抗体的检测、血清中癌症相关蛋白质的存在，或血浆中作为游离DNA出现的肿瘤特异性基因组变化的存在。实施非侵入性诊断方法来检测早期癌症可能会为医生提供癌症证据，但问题是这些信息将如何影响临床干预途径。体外诊断癌症测试阳性结果的确认可能涉及相对侵入性的程序以建立真正的癌症诊断。如果体外诊断测试被证明既具有特异性，即由于无关情况很少产生假阳性结果，又具有足够的敏感性，即很少产生假阴性结果，那么这种筛查测试就有可能通过方便且非侵入性的手段利用多个与疾病相关的靶点进行早期检测和个性化治疗。在这里，我们讨论临床多种分析物生物标志物检测开发中固有的技术和监管障碍。
