J Korean Surg Soc.  2012 May;82(5):271-280.

Gene expression profiling of papillary thyroid carcinomas in Korean patients by oligonucleotide microarrays

• Chung KW
• Kim SW
• Kim SW

Abstract

PURPOSE
The incidence of papillary thyroid carcinomas (PTCs) is rapidly increasing in Korea. Analyzing the gene expression profiling (GEP) of PTCs will facilitate the advent of new methods in diagnosis, prognostication, and treatment. We performed this study to find the GEP of Korean PTCs.
METHODS
We performed oligonucleotide microarray analysis with 19 PTCs and 7 normal thyroid glands. Differentially expressed genes were selected using a t-test (|fold| >3) and adjusted Benjamini-Hochberg false discovery rate P-value < 0.01. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was used to validate microarray data. A classification model was developed by support vector machine (SVM) algorithm to diagnose PTCs based on molecular signatures.
RESULTS
We identified 79 differentially expressed genes (70 up-regulated and 9 down-regulated) according to the criteria. QRT-PCR for five genes (CDH3, NGEF, PROS1, TGFA, MET) was confirmatory of the microarray data. Hierarchical cluster analysis and a classification model by the SVM algorithm accurately differentiated PTCs from normal thyroid gland based on GEP.
CONCLUSION
A disease classification model showed excellent accuracy in diagnosing PTCs, thus showing the possibility of molecular diagnosis in the future. This GEP could serve as baseline data for further investigation in the management of PTCs based on molecular signatures.

Keyword

Thyroid neoplasms; Papillary; Microarray; Gene expression profiling

MeSH Terms

Factor IX
Gene Expression
Gene Expression Profiling
Humans
Incidence
Korea
Oligonucleotide Array Sequence Analysis
Support Vector Machine
Thyroid Gland
Thyroid Neoplasms
Factor IX

Figure

• 

  Fig. 1 Molecular characteristics of differentially expressed genes between papillary thyroid carcinomas and normal thyroid glands. (A) Molecular characteristics according to biological process (B) molecular characteristics according to molecular function.

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  Fig. 2 Hierarchical cluster analysis of genes associated with papillary thyroid carcinomas (PTCs). Columns represent 19 PTCs and 7 normal thyroid glands (controls). Rows show the 79 differentially expressed genes between PTCs and controls. The heatmap indicates up-regulation (red), down-regulation (green) and average (black) gene expression.

• 

  Fig. 3 Validation of microarray analysis by quantitative reverse transcription-polymerase chain reaction (QRT-PCR). Expression status was well-matched with QRT-PCR results, with the exception of non-equilibrium Green's function (NEGF). However, NEGF expression was up-regulated in oligonucleotide microarray analysis and QRT-PCR results. CDH3, cadherin 3, type 1, P-cadherin; NGEF, neuronal guanine nucleotide exchange factor; MET, met proto-oncogene; PROS1, protein S; TGFA, transforming growth factor alpha.

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