Cerutti Janete M, Oler Gisele, Michaluart Pedro, Delcelo Rosana, Beaty Robert M, Shoemaker Jennifer, Riggins Gregory J
Department of Neurosurgery, Johns Hopkins University Medical School, Baltimore, Maryland, USA.
Cancer Res. 2007 Aug 15;67(16):7885-92. doi: 10.1158/0008-5472.CAN-06-4771.
Biomarkers of papillary thyroid carcinoma (PTC) metastasis can accurately identify metastatic cells and aggressive tumor behavior. To find new markers, serial analysis of gene expression (SAGE) was done on three samples from the same patient: normal thyroid tissue, primary PTC, and a PTC lymph node metastasis. This genomewide expression analysis identified 31 genes expressed in lymph node metastasis, but not in the primary tumor. Eleven genes were evaluated by quantitative real-time reverse transcription-PCR (qPCR) on independent sets of matched samples to find genes that were consistently different between the tumor and metastatic samples. LIMD2 and PTPRC (CD45) showed a statistically significant difference in expression between tumor and metastatic samples (P < 0.0045), and an additional gene (LTB) had borderline significance. PTPRC and LTB were tested by immunohistochemistry in an independent set of paired samples, with both markers showing a difference in protein expression. All 20 metastases from 6 patients showed expression in both markers, with little or no expression in primary tumor. Some of these markers could provide an improved means to detect metastatic PTC cells during initial staging of a newly diagnosed carcinoma and/or to rule out recurrence. The functional role of these genes may also provide insight into mechanisms of thyroid cancer metastasis.
甲状腺乳头状癌（PTC）转移的生物标志物能够准确识别转移细胞和侵袭性肿瘤行为。为了寻找新的标志物，对同一患者的三个样本进行了基因表达系列分析（SAGE）：正常甲状腺组织、原发性PTC和PTC淋巴结转移灶。这种全基因组表达分析确定了31个在淋巴结转移灶中表达但在原发性肿瘤中不表达的基因。通过定量实时逆转录PCR（qPCR）对独立的匹配样本集评估了11个基因，以寻找在肿瘤样本和转移样本之间始终存在差异的基因。LIMD2和PTPRC（CD45）在肿瘤样本和转移样本之间的表达存在统计学显著差异（P < 0.0045），另一个基因（LTB）具有临界显著性。通过免疫组织化学在一组独立的配对样本中对PTPRC和LTB进行了检测，两种标志物均显示出蛋白质表达的差异。来自6名患者的所有20个转移灶在两种标志物中均有表达，而原发性肿瘤中表达很少或无表达。这些标志物中的一些可以为在新诊断癌症的初始分期期间检测转移性PTC细胞和/或排除复发提供更好的方法。这些基因的功能作用也可能为甲状腺癌转移机制提供见解。
