Aldred Micheala A, Huang Ying, Liyanarachchi Sandya, Pellegata Natalia S, Gimm Oliver, Jhiang Sissy, Davuluri Ramana V, de la Chapelle Albert, Eng Charis
Human Cancer Genetics Program, The Ohio State University, Columbus, OH 43210, USA.
J Clin Oncol. 2004 Sep 1;22(17):3531-9. doi: 10.1200/JCO.2004.08.127.
We have previously conducted independent microarray expression analyses of the two most common types of nonmedullary thyroid carcinoma, namely papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). In this study, we sought to combine our data sets to shed light on the similarities and differences between these tumor types.
Microarray data from six PTCs, nine FTCs, and 13 normal thyroid samples were normalized to remove interlaboratory variability and then analyzed by unsupervised clustering, t test, and by comparison of absolute and change calls. Expression changes in four genes not previously implicated in thyroid carcinogenesis were verified by reverse transcriptase polymerase chain reaction on these same samples, together with eight additional FTC tumors.
PTCs showed two distinct groups of genes that were either over- or underexpressed compared with normal thyroid, whereas the predominant changes in FTCs were of decreased expression. Five genes could collectively distinguish the two tumor types. PTCs showed overexpression of CITED1, claudin-10 (CLDN10), and insulin-like growth factor binding protein 6 (IGFBP6) but showed no change in expression of caveolin-1 (CAV1) or -2 (CAV2); conversely, FTCs did not express CLDN10 and had decreased expression of IGFBP6 and/or CAV1 and CAV2.
PTC and FTC show distinctive microarray expression profiles, suggesting that either they have different molecular origins or they diverge distinctly from a common origin. Furthermore, if verified in a larger series of tumors, these genes could, in combination with known tumor-specific chromosome translocations, form the basis of a valuable diagnostic tool.
我们之前对两种最常见的非髓样甲状腺癌,即乳头状甲状腺癌(PTC)和滤泡状甲状腺癌(FTC)进行了独立的基因芯片表达分析。在本研究中,我们试图合并我们的数据集,以阐明这些肿瘤类型之间的异同。
对来自6例PTC、9例FTC和13例正常甲状腺样本的基因芯片数据进行标准化处理,以消除实验室间的差异,然后通过无监督聚类、t检验以及绝对和变化调用的比较进行分析。在这些相同样本以及另外8例FTC肿瘤上,通过逆转录聚合酶链反应验证了4个先前未涉及甲状腺癌发生的基因的表达变化。
与正常甲状腺相比,PTC显示出两组不同的基因,一组过表达,一组低表达,而FTC的主要变化是表达降低。5个基因可以共同区分这两种肿瘤类型。PTC显示CITED1、claudin-10(CLDN10)和胰岛素样生长因子结合蛋白6(IGFBP6)过表达,但小窝蛋白-1(CAV1)或-2(CAV2)的表达没有变化;相反,FTC不表达CLDN10,IGFBP6和/或CAV1及CAV2的表达降低。
PTC和FTC显示出独特的基因芯片表达谱,表明它们要么有不同的分子起源,要么从共同起源明显分化。此外,如果在更大系列的肿瘤中得到验证,这些基因与已知的肿瘤特异性染色体易位相结合,可能构成一种有价值的诊断工具的基础。