Griffith Obi L, Melck Adrienne, Jones Steven J M, Wiseman Sam M
Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada.
J Clin Oncol. 2006 Nov 1;24(31):5043-51. doi: 10.1200/JCO.2006.06.7330.
An estimated 4% to 7% of the population will develop a clinically significant thyroid nodule during their lifetime. In many cases, preoperative diagnoses by needle biopsy are inconclusive. Thus, there is a clear need for improved diagnostic tests to distinguish malignant from benign thyroid tumors. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers from numerous thyroid cancer expression profiling studies.
To address this challenge, we have carried out a comprehensive meta-review of thyroid cancer biomarkers from 21 published studies. A gene ranking system that considers the number of comparisons in agreement, total number of samples, average fold-change and direction of change was devised.
We have observed that genes are consistently reported by multiple studies at a highly significant rate (P < .05). Comparison with a meta-analysis of studies reprocessed from raw data showed strong concordance with our method.
Our approach represents a useful method for identifying consistent gene expression markers when raw data are unavailable. A review of the top 12 candidates revealed well known thyroid cancer markers such as MET, TFF3, SERPINA1, TIMP1, FN1, and TPO as well as relatively novel or uncharacterized genes such as TGFA, QPCT, CRABP1, FCGBP, EPS8 and PROS1. These candidates should help to develop a panel of markers with sufficient sensitivity and specificity for the diagnosis of thyroid tumors in a clinical setting.
估计有4%至7%的人口在其一生中会出现具有临床意义的甲状腺结节。在许多情况下，针吸活检的术前诊断并不明确。因此，迫切需要改进诊断测试以区分甲状腺恶性肿瘤和良性肿瘤。高通量分子分析技术的最新发展应能实现对新诊断标志物的快速评估。然而，研究人员面临着来自众多甲状腺癌表达谱研究的大量潜在标志物。
为应对这一挑战，我们对21项已发表研究中的甲状腺癌生物标志物进行了全面的荟萃综述。设计了一种基因排名系统，该系统考虑了一致比较的数量、样本总数、平均倍数变化和变化方向。
我们观察到多个研究一致报告的基因具有高度显著性（P <.05）。与对原始数据重新处理后的研究进行的荟萃分析相比，我们的方法显示出很强的一致性。
当无法获得原始数据时，我们的方法是识别一致基因表达标志物的有用方法。对前12名候选基因的综述揭示了众所周知的甲状腺癌标志物，如MET、TFF3、SERPINA1、TIMP1、FN1和TPO，以及相对新颖或未表征的基因，如TGFA、QPCT、CRABP1、FCGBP、EPS8和PROS1。这些候选基因应有助于开发一组在临床环境中对甲状腺肿瘤诊断具有足够敏感性和特异性的标志物。
