Fryknäs Mårten, Wickenberg-Bolin Ulrika, Göransson Hanna, Gustafsson Mats G, Foukakis Theodoros, Lee Jia-Jing, Landegren Ulf, Höög Anders, Larsson Catharina, Grimelius Lars, Wallin Göran, Pettersson Ulf, Isaksson Anders
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Tumour Biol. 2006;27(4):211-20. doi: 10.1159/000093056. Epub 2006 May 2.
To identify molecular markers useful for the diagnostic discrimination of benign and malignant follicular thyroid tumors.
A panel of thyroid tumors was characterized with expression profiling using cDNA microarrays. A robust algorithm for gene selection was developed to identify molecular markers useful for the classification of heterogeneous tumor classes. The study included tumor tissue specimens from 10 patients with benign follicular adenomas and from 10 with malignant tumors. The malignant tumors mainly consisted of clinically relevant minimally invasive follicular carcinomas. The mRNA expression level of a candidate gene, FHL1, was evaluated in an independent series of 61 tumors.
22 gene expression markers were identified as differentially expressed. Several of the identified genes, for example DIO1, CITED1, CA12 and FN1, have previously been observed as differentially expressed in various thyroid tumors. FHL1 was significantly underexpressed in carcinomas compared to adenomas in the independent panel of tumors. The results indicate that a small number of genes can be useful to distinguish follicular adenomas from follicular carcinomas.
Our findings clearly corroborate previous studies and identify novel candidate molecular markers. These genes have the potential for molecular classification of follicular thyroid tumors and for providing improved understanding of the molecular mechanisms involved in thyroid malignancies.
鉴定有助于鉴别甲状腺滤泡状良性和恶性肿瘤的分子标志物。
使用cDNA微阵列对一组甲状腺肿瘤进行表达谱分析。开发了一种强大的基因选择算法，以鉴定有助于对异质性肿瘤类别进行分类的分子标志物。该研究包括10例良性滤泡性腺瘤患者和10例恶性肿瘤患者的肿瘤组织标本。恶性肿瘤主要由具有临床相关性的微侵袭性滤泡癌组成。在一个独立的包含61个肿瘤的系列中评估了候选基因FHL1的mRNA表达水平。
鉴定出22个差异表达的基因表达标志物。一些已鉴定的基因，例如DIO1、CITED1、CA12和FN1，先前已在各种甲状腺肿瘤中观察到差异表达。在独立肿瘤组中，与腺瘤相比，FHL1在癌中显著低表达。结果表明，少数基因可用于区分滤泡性腺瘤和滤泡癌。
我们的发现明确证实了先前的研究，并鉴定出了新的候选分子标志物。这些基因具有对甲状腺滤泡状肿瘤进行分子分类以及更好地理解甲状腺恶性肿瘤相关分子机制的潜力。
