Yano Yukiko, Uematsu Naoya, Yashiro Tohru, Hara Hisato, Ueno Ei, Miwa Masanao, Tsujimoto Gozoh, Aiyoshi Yuji, Uchida Kazuhiko
Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Clin Cancer Res. 2004 Mar 15;10(6):2035-43. doi: 10.1158/1078-0432.ccr-0807-03.
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.
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.
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.
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.
癌症的诊断和治疗通常基于临床相关标志物，这些标志物在恶性组织中特异性表达，且表达水平高于正常组织。我们通过使用cDNA微阵列监测甲状腺乳头状癌（PTC）特异性基因表达，来检测PTC的潜在标志物。
使用人类4000基因cDNA微阵列比较PTC组织、正常甲状腺组织和健康外周血细胞的基因表达谱。通过免疫组织化学检测PTC中上调基因在甲状腺组织中的蛋白表达。
相对于正常甲状腺组织和健康外周血细胞，PTC组织中有64个基因过度表达。PTC中上调的基因参与细胞周期调控、DNA损伤反应、血管生成和肿瘤发生。在这些基因中，碱性成纤维细胞生长因子和血小板衍生生长因子通过免疫化学方法被鉴定为在甲状腺肿瘤中特异性高水平表达的蛋白。已被鉴定为PTC生物标志物的碱性成纤维细胞生长因子，在54%的PTC病例、67%的甲状腺滤泡癌和36%的良性甲状腺肿瘤中过度表达。血小板衍生生长因子在81%的PTC病例和100%的滤泡癌中过度表达，但在正常甲状腺组织和良性甲状腺肿瘤中免疫阴性。
血小板衍生生长因子可能是PTC和滤泡癌的潜在生物标志物。使用微阵列进行表达谱分析，随后进行免疫组织化学研究，可用于促进癌症分子生物标志物的开发。
