Selaru Florin M, Xu Yan, Yin Jing, Zou Tong, Liu Thomas C, Mori Yuriko, Abraham John M, Sato Fumiaki, Wang Suna, Twigg Charlie, Olaru Andreea, Shustova Valentina, Leytin Anatoly, Hytiroglou Prodromos, Shibata David, Harpaz Noam, Meltzer Stephen J
Department of Medicine, Division of Gastroenterology and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Gastroenterology. 2002 Mar;122(3):606-13. doi: 10.1053/gast.2002.31904.
BACKGROUND & AIMS: There is a subtle distinction between sporadic colorectal adenomas and cancers (SAC) and inflammatory bowel disease (IBD)-associated dysplasias and cancers. However, this distinction is clinically important because sporadic adenomas are usually managed by polypectomy alone, whereas IBD-related high-grade dysplasias mandate subtotal colectomy. The current study evaluated the ability of artificial neural networks (ANNs) based on complementary DNA (cDNA) microarray data to discriminate between these 2 types of colorectal lesions.
We hybridized cDNA microarrays, each containing 8064 cDNA clones, to RNAs derived from 39 colorectal neoplastic specimens. Hierarchical clustering was performed, and an ANN was constructed and trained on a set of 5 IBD-related dysplasia or cancer (IBDNs) and 22 SACs.
Hierarchical clustering based on all 8064 clones failed to correctly categorize the SACs and IBDNs. However, the ANN correctly diagnosed 12 of 12 blinded samples in a test set (3 IBDNs and 9 SACs). Furthermore, using an iterative process based on the computer programs GeneFinder, Cluster, and MATLAB, we reduced the number of clones used for diagnosis from 8064 to 97. Even with this reduced clone set, the ANN retained its capacity for correct diagnosis. Moreover, cluster analysis performed with these 97 clones now separated the 2 types of lesions.
Our results suggest that ANNs have the potential to discriminate among subtly different clinical entities, such as IBDNs and SACs, as well as to identify gene subsets having the power to make these diagnostic distinctions.
散发性结直肠腺瘤和癌(SAC)与炎症性肠病(IBD)相关发育异常及癌之间存在细微差别。然而,这种差别在临床上很重要,因为散发性腺瘤通常仅通过息肉切除术处理,而IBD相关的高级别发育异常则需要进行次全结肠切除术。本研究评估了基于互补DNA(cDNA)微阵列数据的人工神经网络(ANN)区分这两种结直肠病变的能力。
我们将每个包含8064个cDNA克隆的cDNA微阵列与来自39个结直肠肿瘤标本的RNA进行杂交。进行层次聚类,并在一组5个IBD相关发育异常或癌(IBDN)和22个SAC上构建并训练一个ANN。
基于所有8064个克隆的层次聚类未能正确分类SAC和IBDN。然而,ANN在一个测试集中正确诊断了12个盲法样本中的12个(3个IBDN和9个SAC)。此外,使用基于计算机程序GeneFinder、Cluster和MATLAB的迭代过程,我们将用于诊断的克隆数量从8064个减少到97个。即使使用这个减少后的克隆集,ANN仍保留其正确诊断的能力。此外,用这97个克隆进行的聚类分析现在将这两种病变区分开来。
我们的结果表明,ANN有潜力区分细微不同的临床实体,如IBDN和SAC,以及识别具有进行这些诊断区分能力的基因子集。