Chung Ki-Wook, Kim Seok Won, Kim Sun Wook
Center for Thyroid Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
J Korean Surg Soc. 2012 May;82(5):271-80. doi: 10.4174/jkss.2012.82.5.271. Epub 2012 Apr 26.
The incidence of papillary thyroid carcinomas (PTCs) is rapidly increasing in Korea. Analyzing the gene expression profiling (GEP) of PTCs will facilitate the advent of new methods in diagnosis, prognostication, and treatment. We performed this study to find the GEP of Korean PTCs.
We performed oligonucleotide microarray analysis with 19 PTCs and 7 normal thyroid glands. Differentially expressed genes were selected using a t-test (|fold| >3) and adjusted Benjamini-Hochberg false discovery rate P-value < 0.01. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was used to validate microarray data. A classification model was developed by support vector machine (SVM) algorithm to diagnose PTCs based on molecular signatures.
We identified 79 differentially expressed genes (70 up-regulated and 9 down-regulated) according to the criteria. QRT-PCR for five genes (CDH3, NGEF, PROS1, TGFA, MET) was confirmatory of the microarray data. Hierarchical cluster analysis and a classification model by the SVM algorithm accurately differentiated PTCs from normal thyroid gland based on GEP.
A disease classification model showed excellent accuracy in diagnosing PTCs, thus showing the possibility of molecular diagnosis in the future. This GEP could serve as baseline data for further investigation in the management of PTCs based on molecular signatures.
韩国甲状腺乳头状癌(PTC)的发病率正在迅速上升。分析PTC的基因表达谱(GEP)将有助于诊断、预后和治疗新方法的出现。我们开展这项研究以找出韩国PTC的GEP。
我们对19例PTC和7个正常甲状腺进行了寡核苷酸微阵列分析。使用t检验(|倍数|>3)和调整后的Benjamini-Hochberg错误发现率P值<0.01来选择差异表达基因。采用定量逆转录聚合酶链反应(QRT-PCR)验证微阵列数据。通过支持向量机(SVM)算法建立分类模型,基于分子特征诊断PTC。
根据标准,我们鉴定出79个差异表达基因(70个上调和9个下调)。对五个基因(CDH3、NGEF、PROS1、TGFA、MET)进行的QRT-PCR证实了微阵列数据。基于GEP的层次聚类分析和SVM算法分类模型准确地区分了PTC和正常甲状腺。
疾病分类模型在诊断PTC方面显示出优异的准确性,从而显示了未来分子诊断的可能性。该GEP可为基于分子特征的PTC管理进一步研究提供基线数据。