Gene expression profiling identifies platelet-derived growth factor as a diagnostic molecular marker for papillary thyroid carcinoma.
OBJECTIVE
Cancer diagnostics and therapeutics are often based on clinically relevant markers that are expressed specifically in a malignant tissue at levels higher than in normal tissue. We examined potential markers for papillary thyroid carcinoma (PTC) by monitoring PTC-specific gene expression using cDNA microarray.


METHODS
Gene expression profiles for PTC tissue, normal thyroid tissue, and healthy peripheral blood cells were compared by use of a human 4000-gene cDNA microarray. Protein expressions of the up-regulated genes in PTC were examined in thyroid tissues by immunohistochemistry.


RESULTS
Sixty-four genes were overexpressed in PTC tissue relative to normal thyroid tissue and healthy peripheral blood cells. The genes that were up-regulated in PTC were involved in cell cycle regulation, DNA damage response, angiogenesis, and oncogenesis. Among these genes, basic fibroblast growth factor and platelet-derived growth factor were identified by immunochemical methods as proteins that are specifically expressed at high levels in thyroid neoplasms. Basic fibroblast growth factor, which has been identified as a biomarker for PTC, was overexpressed in 54% of PTC cases, 67% of follicular thyroid carcinomas, and 36% of benign thyroid neoplasms. Platelet-derived growth factor was overexpressed in 81% of PTC cases and 100% of follicular carcinomas, but was immunonegative in normal thyroid tissues and benign thyroid neoplasms.


CONCLUSIONS
Platelet-derived growth factor may be a potential biomarker for PTC and follicular carcinoma. Expression profile analysis using a microarray followed by immunohistochemical study can be used to facilitate the development of molecular biomarkers for cancer.
Yano
Yukiko
Y
Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Uematsu
Naoya
N
Yashiro
Tohru
T
Hara
Hisato
H
Ueno
Ei
E
Miwa
Masanao
M
Tsujimoto
Gozoh
G
Aiyoshi
Yuji
Y
Uchida
Kazuhiko
K
D002291:Carcinoma, Papillary / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D012016:Reference Values; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D005819:Genetic Markers; D010982:Platelet-Derived Growth Factor