title: Artificial neural networks and gene filtering distinguish between global gene expression profiles of Barrett's esophagus and esophageal cancer.
abstract: cDNAmicroarrays, combined with bioinformatics analyses, are becomingincreasingly used in current medical research. Existing analytic methods,particularly those that are unsupervised, often have difficulty recognizing subtle differences among predefined subgroups. In contrast, supervised methods, such as Artificial Neural Networks (ANNs), are able to recognize subtly different biological entities. We applied ANNs in a proof-of-principle study of cDNA microarray data in esophageal cancer (CA) and premalignancy. cDNA microarrays, each containing 8064 clones, were hybridized to RNAs from 22 esophageal lesions, including 14 Barrett's esophagus (BA) metaplasias and 8 esophageal carcinomas (3 squamous cell carcinomas and 5 adenocarcinomas). Scanned cDNA microarray data were analyzed using the bioinformatics software Cluster/TreeView, Significance Analysis of Microarrays (SAM), and ANNs. Cluster analysis based on all 8064 clones on the microarrays was unable to correctly distinguish BA specimens from CA specimens. SAM then selected 160 differentially expressed genes between Barrett's and cancer. Cluster analysis based on this reduced set still misclassified 2 Barrett's as cancers. The ANN was trained on 12 samples and tested against the remaining 10 samples. Using the 160 selected genes, the ANN correctly diagnosed all 10 samples in the test set. Finally, the 160 genes selected by SAM may merit further study as biomarkers of neoplastic progression in the esophagus, as well as in elucidating pathological mechanisms underlying BA and CA.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore VA Hospital, 21201, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Florin M
authors.initials: FM
authors.lastname: Selaru
authors.forename: Jing
authors.initials: J
authors.lastname: Yin
authors.forename: Tong Tong
authors.initials: TT
authors.lastname: Zou
authors.forename: Valentina
authors.initials: V
authors.lastname: Shustova
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Mori
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Liu
authors.forename: Andreea
authors.initials: A
authors.lastname: Olaru
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.forename: Martha C
authors.initials: MC
authors.lastname: Kimos
authors.forename: Kellie
authors.initials: K
authors.lastname: Perry
authors.forename: Kena
authors.initials: K
authors.lastname: Desai
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Greenwald
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Krasna
authors.forename: David
authors.initials: D
authors.lastname: Shibata
authors.forename: John M
authors.initials: JM
authors.lastname: Abraham
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D005810:Multigene Family; D016571:Neural Networks, Computer; D020411:Oligonucleotide Array Sequence Analysis