Meta- and reanalysis of gene expression profiles of hot and cold thyroid nodules and papillary thyroid carcinoma for gene groups.
BACKGROUND
There are an increasing number of studies analyzing gene expression profiles in various benign and malignant thyroid tumors. This creates the opportunity to validate results obtained from one microarray study with those from other data sets. This process requires rigorous methods for accurate comparison.


OBJECTIVE
The ability to compare data sets derived from different Affymetrix GeneChip generations and the influence of intra- and interindividual comparisons of gene expression data were evaluated to build multigene classifiers of benign thyroid nodules to verify a previously proposed papillary thyroid carcinoma (PTC) classifier and to look for molecular pathways essential for PTC oncogenesis.


METHODS
Gene expression profile data sets from autonomously functioning and cold thyroid nodules and from PTC were analyzed by support vector machines. GenMAPP analysis was used for PTC data analysis to examine the expression patterns of biologically relevant gene sets.


RESULTS
Only intraindividual reference samples allowed the identification of subtle changes in the expression patterns of relevant signaling cascades, such as the MAPK pathway in PTC. Using an artificial intelligence approach, the autonomously functioning and cold thyroid nodule multigene classifiers were derived and evaluated by cross-comparisons.


CONCLUSIONS
We recommend defining classifiers within one generation of gene chips and subsequently checking them across different array generations. Using this approach, we have demonstrated the specificity of a previously reported PTC classifier on an independent collection of benign tumors. Moreover, we propose multigene classifiers for different types of benign thyroid nodules.
Eszlinger
Markus
M
III. Medical Department, University of Leipzig, Philipp-Rosenthal-Strasse 27, D-04103 Leipzig, Germany.
Wiench
Małgorzata
M
Jarzab
Barbara
B
Krohn
Knut
K
Beck
Martin
M
Läuter
Jürgen
J
Gubała
Elzbieta
E
Fujarewicz
Krzysztof
K
Swierniak
Andrzej
A
Paschke
Ralf
R
D000465:Algorithms; D001185:Artificial Intelligence; D002291:Carcinoma, Papillary / Q000145:classification / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000145:classification / Q000235:genetics*; D016606:Thyroid Nodule / Q000145:classification / Q000235:genetics*